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. The parents may view the crying as evidence of illness or as a problem of their caregiving ability. 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.

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.

Few people agree about how much crying is considered excessive. the approximate 95th percentile duration of daily crying ranged from:

  • 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. 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.

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”). 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.
  • 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.
  • 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 (e.g., louder, higher and more variable in pitch, more dysphonic); associated with features of hypertonia; inconsolability

EPIDEMIOLOGY

Estimates of the prevalence of colic in infants range from 8 to 40 percent. The wide range is due to differences in diagnostic criteria, study design, populations, and family perceptions of “excessive and prolonged” crying.

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. It appears to be more common in industrialized countries, White infants, and in areas that are further away from the equator.

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. 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.

PROPOSED ETIOLOGIES

The etiology of colic is unknown. It probably represents a final common pathway for numerous contributing factors. 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. 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”. 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 suggest hydrolysate formulas or a hypoallergenic diet for breastfeeding mothers may reduce distress in infants with colic
  • 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.
  • 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.
  • Intestinal hypermotility– Evidence supporting an association between intestinal hypermotility due to autonomic imbalance is contradictory. In observational studies, motilin concentrations are increased in infants with colic, but vasoactive intestinal peptide and gastrin concentrations are not. 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 Klebsiellaspecies, anaerobic gram-negative bacteria, coliform bacteria (including Escherichia coli), and Lactobacillus species (L. brevis and L. lactis). Observational studies have also noted an association between colic and gut inflammation (as indicated by increased fecal calprotectin) and altered gut microbiota. Others have noted decreased fecal calprotectin levels as colicky symptoms improved over time or in response to Lactobacillus reuteri therapy.

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)

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. 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). 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. 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.
  • 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.
  • 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; colic was not associated with an increased risk of migraine with aura. These findings confirm those of retrospective studies, although it is not clear whether infantile colic is an early manifestation of childhood migraine or a marker of migraine genetics.
  • 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. Evidence supporting this theory is limited. The most direct evidence comes from therapeutic trials aimed at modifying parental behavior. 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. 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).
  • 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.

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. 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.

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.

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

  • Paroxysms– The cry/fuss behavior of colic generally is paroxysmal. 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. Colicky crying may sound as if the infant is in pain or is screaming rather than crying. 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.
  • Hypertonia– Episodes of colic may be associated with physical characteristics associated with hypertonia. 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. 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.

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 (see table). This distinction usually can be made with history and physical examination.

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.

Selected identifiable causes of prolonged/excessive crying in an infant younger than four months of age.

Condition Clinical features
General
Drug ingestion or overdosage (eg, pseudoephedrine) History of medication administration
Hunger/inadequate feeding Signs of hypovolemia or undernutrition (eg, sunken fontanelle, dry mucous membranes, decreased subcutaneous fat, etc)
Neonatal abstinence syndrome Maternal history of prenatal substance use or positive urine screen (maternal or infant)
Skin
Hair tourniquet of digit or penis Apparent on physical examination
 diaper rash Apparent on physical examination
Trauma (abusive or nonabusive) Bruising, laceration
Eyes
Corneal abrasion or foreign body May have photophobia, positive fluorescein examination
Glaucoma Chronic or intermittent tearing, photophobia, corneal enlargement, corneal clouding, optic nerve cupping, ocular enlargement
Ears, nose, oropharynx
Otitis media Bulging tympanic membrane
Thrush White plaques on the buccal mucosa, tongue, or palate
Cardiovascular
Anomalous origin of the left coronary artery Cardiomegaly, heart failure
Heart failure Feeding intolerance, tachycardia, poor perfusion, tachypnea
Supraventricular tachycardia Pallor, irritability, poor feeding, cyanosis, restlessness
Gastrointestinal
Anal fissures Apparent on physical examination
Constipation Passage of hard stools
Gastroesophageal reflux Vomiting, poor weight gain, feeding refusal, gross or occult blood in the stool
Gastrointestinal obstruction (eg, pyloric stenosis, intussusception, volvulus) Vomiting (may or may not be bilious or forceful), gastrointestinal bleeding, forceful vomiting, abdominal tenderness, distension, right-sided sausage-shaped abdominal mass (intussusception), palpable “olive” (pyloric stenosis)
Inguinal hernia Bulge in the groin area (may be intermittent), vomiting and abdominal distension may indicate incarceration
Genitourinary
Meatal ulcer Apparent on examination
Ovarian torsion Feeding intolerance, vomiting, abdominal distension, fussiness/irritability
Testicular torsion Acute testicular swelling and tenderness
Urinary tract infection Fever, suprapubic tenderness, poor feeding, poor weight gain
Urinary tract obstruction Abdominal distension (due to enlarged bladder), difficulty voiding, poor urinary stream, straining or grunting during voiding
Skeletal
Fracture Decreased movement of extremity, asymmetric Moro reflex, localized swelling and crepitation, increased pain response with movement of the extremity
Osteomyelitis or septic arthritis Fever, decreased movement of extremity, asymmetric Moro reflex, increased pain response with movement of the extremity
Neurologic
Abusive head trauma Seizures, respiratory difficulty or apnea, retinal hemorrhages, cutaneous bruising, associated injuries
Meningitis Fever, bulging fontanelle, lethargy, irritability, meningismus (often not present in infants)
Neuromuscular disease, CNS disorder, metabolic disease Abnormal tone, muscular weakness

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). 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, as well as psychosocial factors that may be contributing to it.

Important aspects of the history in a child with colic include:

  • The infant’s feeding, stooling, urination, and sleeping patterns, including vomiting (helpful in evaluating the possibility of gastrointestinal, cardiovascular, and metabolic conditions)
  • Bloody stool may indicate cow’s milk or soy-induced colitis, anal fissure, intussusception
  • Bilious or projectile vomiting may indicate gastrointestinal obstruction (eg, pyloric stenosis, volvulus)
  • Prenatal and perinatal history, including risk factors for sepsis (eg, premature rupture of membranes, maternal fever, maternal colonization with group B Streptococcus)
  • 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
  • Specific questions about the crying or fussiness, including:
  • 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).
  • How long does the crying last? – Duration of crying may help to differentiate normal infant crying from colic.
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.

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

  • 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)
  • Assessment of temperament (eg, sensitivity, irritability, soothability, intensity, adaptability) 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
  • Assessment for identifiable causes of prolonged crying in infants, including:
  • Assessment of hydration and subcutaneous fat (to evaluate adequacy of feeding)

•Assessment for tongue-tie, which may be associated with breastfeeding problems

Abnormally short frenulum, inserting at the tip of the tongue in a neonate.

  • Eye examination for foreign body, corneal abrasion, infantile glaucoma (eg, corneal enlargement or clouding), retinal hemorrhage (though fundoscopic examination may be difficult)

Corneal enlargement in congenital glaucoma

The right cornea is larger than the left.

  • Ear examination for otitis media

Bulging tympanic membrane in acute otitis media

Examples of the white, bulging tympanic membrane seen in acute otitis media.
(A) A bulging tympanic membrane with minimal erythema.
(B) Tympanic membrane bulging, marked erythema along the handle of the malleus, and an air-fluid level in the anterosuperior portion of the tympanic membrane.

  • Oropharyngeal examination for thrush

Three examples of thrush (oral candidiasis) in an infant

Note the white plaques on the inner lip and tongue (A) and on the buccal mucosa (B and C).

  • Cardiovascular evaluation for signs of heart failure or supraventricular tachycardia (eg, tachycardia, tachypnea, poor perfusion, S3 gallop, tachypnea)
  • Evaluation of the abdomen for tenseness, absence of bowel sounds (possible clues to an acute abdominal process such as intussusception, volvulus)
  • Evaluation of perineum for diaper rash, testicular torsion, hair tourniquet, meatal ulcer, anal fissure, inguinal hernia
  • 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, bruising or petechiae, decreased range of motion, and pain with passive movement

Superficial hair tourniquet

Infant brought in by mother who noticed toe was red and swollen while bathing child. Note the grossly visible hair tourniquet at the base of the fourth toe. It was removed using fine forceps without difficulty and with return of normal appearance of the toe within 24 hours.

  • 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

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.

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. In addition, observational studies suggest that infantile colic is associated with increased risk of postpartum depression and early cessation of breastfeeding.

MANAGEMENT

Overview — Management of the otherwise well infant with prolonged or excessive crying is individualized based upon the history, examination, and family characteristics. Some caregivers and families tolerate crying better than others.

Interventions are targeted to decrease crying and bolster the infant-family relationship. The goals of management are to help the caregivers cope with the child’s symptoms and to prevent long-term sequelae in the caregiver-child relationship.

Caregiver support is the mainstay of management. First-line interventions consist of addressing feeding problems and suggesting techniques to soothe the infant and/or decrease environmental stimuli. Caregivers can be encouraged to experiment with these interventions to see which, if any, work. Although the evidence supporting first-line interventions is limited, they are inexpensive, unlikely to be harmful, and may be helpful for caregivers who find it hard to have nothing to do while awaiting spontaneous remission (which confirms the diagnosis).

Several interventions for colic have been evaluated in randomized trials; however, most of the trials had methodologic weaknesses (eg, small sample size, inadequate blinding). The lack of strong supporting evidence for any one strategy, combined with the number of proposed etiologies, may lead practitioners to recommend a variety of interventions, alone or in combination. Each of the soothing techniques may work in some infants or in a given infant, some of the time, but none of the interventions work all of the time.

Caregiver support and education — Caregiver support is the mainstay of the management of colic. It may influence the way the caregivers view their ability to care for their child.

Important aspects of caregiver education and support include:

  • Education that colic is common and usually resolves spontaneously by three to four months of age.
  • Reassurance that the infant is not sick. This may require frequent follow-up (either by phone or in person).
  • Education that colic it is not caused by something that they are doing or not doing. It does not mean that the infant is rejecting them.
  • Acknowledging that the infant is difficult to soothe and that you know that they are doing the best that they can. This is essential in preventing the caregivers from feeling as if they have failed.
  • Providing tips for techniques to soothe the baby.
  • Encouraging the caregivers to take breaks from the crying infant (eg, taking turns with the infant during the colicky period, asking a relative or friend to babysit so that they can have a break, placing the crying infant in their crib) and to have a “rescue” plan (a prearranged plan in which a relative or friend can step in if the caregivers feel overwhelmed).
  • Acknowledging that feelings of frustration, anger, exhaustion, guilt, and helplessness are normal.

Clinical studies of caregiver support/counseling for infantile colic usually find caregiver support/counseling beneficial, but the evidence is limited.

Home-based nursing intervention or contact with other caregivers who have or had infants with colic also may be beneficial.

First-line interventions — As first-line interventions for colic, we suggest changes to the feeding technique and/or experimenting with a number of techniques to soothe the infant. These interventions address some of the potential etiologies of colic (eg, swallowed air, overstimulation). We generally initiate changes to feeding and soothing techniques at the same time, explaining the theories of the etiology of colic that they are meant to address.

Feeding technique — Feeding changes may be helpful for infants whose colic is associated with feeding problems (eg, underfeeding, overfeeding, inadequate burping). Bottle-feeding the baby in a vertical position (using a curved bottle) in combination with frequent burping may reduce swallowed air. Using a bottle with a collapsible bag also may help reduce air swallowing. Changes to breastfeeding technique also may be warranted. However, the management of breastfeeding problems should be individualized. Consultation with a lactation specialist may be warranted.

Soothing techniques — We suggest that caregivers experiment with one or more of the following techniques for soothing the infant and/or decreasing sensory stimulation. They should be instructed to continue those that are helpful and discontinue those that are not. The soothing techniques can be tried in any order and/or combination. Caregivers can be instructed to try a technique for several minutes and if it does not work, move on to another soothing technique. The success or failure of individual soothing techniques may vary from one episode of colic to the next. We suggest that families experiment with soothing techniques for several days to weeks before moving on to other interventions.

  • Using a pacifier.
  • Taking the infant for a ride in the car or a walk in the stroller/buggy.
  • Holding the infant or placing them in a front carrier.
  • Rocking the infant.
  • Changing the scenery (or minimizing visual stimuli).
  • Placing the child in an infant swing.
  • Providing a warm bath.
  • Rubbing the infant’s abdomen.
  • Hip healthy swaddling(ie, with room for hip flexion, knee flexion, and free movement of the legs
  • Playing an audiotape of heartbeats.
  • Providing “white noise” (eg, vacuum cleaner, clothes drier, dishwasher, commercial white noise generator, etc). Commercial white noise generators (sometimes called infant sleep machines) can produce sound pressure levels greater than the recommended noise threshold for infants in hospital nurseries. To minimize potential adverse effects on hearing or auditory development, white noise generators should be placed as far away from the infant as possible, played at a low volume, and used only for short periods of time.

These interventions are suggested by experts. They have not been proven effective in randomized trials but are inexpensive, unlikely to be harmful, involve the caregivers, and may help to reduce caregiver or infant anxiety. In a large observational study, holding, walking, and rocking were found to be effective in calming breastfed infants (with or without colic) younger than 16 weeks.

Unproven interventions — A number of other interventions for infantile colic have been evaluated in randomized trials with methodologic weaknesses or inconsistent results. Given these limitations, we generally do not suggest these interventions for infantile colic. However, they may be suggested for some patients on a case-by-case basis after a discussion of the potential risks and benefits if first-line interventions have been unsuccessful after several days to weeks. Providing a several week trial of first-line interventions allows time for colic to run its natural course and may avoid unnecessary, costly, or potentially harmful remedies.

Dietary changes — A time-limited trial of dietary interventions may be warranted for infants who do not respond to first-line interventions, particularly if milk protein allergy is suspected. Dietary changes vary depending upon whether the infant is formula-fed or breastfed.

Formula-fed infants

  • Extensive hydrolysate formula– A one-week trial of an extensive hydrolysate infant formula is an option for formula-fed infants with colic who have not responded to first line-interventions. A subgroup of infants with colic may have an allergy or intolerance to cow’s milk formula, although infants with allergy or intolerance usually have associated clinical features (eg, bloody stool, vomiting, rash, etc).

Hydrolysate formula may be continued if there is a decrease in crying/fussiness. The response usually occurs within 48 hours. The original formula is resumed if there is no change in the infant’s symptoms (hydrolysate formulas are more expensive than cow’s milk-based formulas).

Systematic reviews of small randomized trials with methodologic limitations suggest that hydrolysate formulas may reduce distress in some infants with colic. Additional studies are necessary to confirm these results.

  • Soy protein formula– We do not suggest changing from cow’s milk to soy protein formula for formula-fed infants with colic. The benefits of soy versus cow’s milk protein in the prevention and management of colic are unproven. Studies comparing the effects of soy and hypoallergenic formulas on the reduction of colicky symptoms are lacking.

Based on four small randomized trials with methodologic limitations (eg, inadequate blinding), a 2012 systematic review concluded that soy protein formulas may improve colic symptoms, but additional studies are necessary.

The American Academy of Pediatrics Committee on Nutrition does not recommend soy protein formula for the treatment of infantile colic.

  • Fiber-enriched formula– We do not suggest fiber-enriched formulas for formula-fed infants with colic. In a randomized crossover trial in 27 term infants in which the investigators were blinded but the caregivers were not, fiber supplementation of soy-protein formula did not affect the average daily duration of crying. However, the caregivers of 18 infants found the fiber-supplemented formula beneficial in alleviating colic symptoms.

Breastfed infants — A time-limited trial of a decrease in maternal milk product consumption or a hypoallergenic maternal diet (eg, no milk, eggs, nuts, wheat) is an option for breastfed infants with colic who have not responded to first-line interventions and whose caregivers have difficulty coping. A subgroup of infants with colic may have food allergy or allergy to cow’s milk, although infants with allergy usually have associated clinical features (eg, rash, wheezing). Maternal dietary changes may be particularly beneficial if the mother is atopic or the baby has symptoms of cow’s milk allergy (eg, eczema, wheezing, diarrhea, or vomiting).

Several systematic reviews of small randomized trials with methodologic limitations suggest that a hypoallergenic diet may reduce distress in infants with colic. Additional studies are necessary to confirm these results.

Probiotics

  • Management
  • Lactobacillus reuteri– We do not suggest L. reuterifor the routine management of colic in breastfed or formula-fed infants. However, for breastfed infants whose caregivers prefer to try probiotics, it may be reasonable to offer L. reuteri DSM 17938 (but not other species or strains) after a discussion of the potential benefits, risks, and uncertainties.

Although there is evidence from randomized trials that treatment with L. reuteri DSM 17938 is associated with decreased crying time, the evidence of benefit is inconsistent and must be weighed against the natural history of improvement over time. Additional factors affecting our suggestion include the cost of probiotics, which are not typically covered by commercial insurance, and uncertain safety of commercially available products. The US Food and Drug Administration does not evaluate probiotic products, which may contain unlabeled ingredients or species that differ from those indicated on the label or be contaminated with fungi or other pathogens). In addition, the reporting of harms in randomized trials of probiotics is often inadequate or lacking.

  • Other probiotics– We do not suggest probiotics other than L. reuterifor the routine management of colic in formula-fed or breastfed infants.
  • Prevention– We do not suggest probiotics (including L. reuteri) for the prevention of colic. Although they appear to be safe and may reduce crying time, clear evidence that they are effective in preventing colic is lacking.

Lactase — We do not suggest lactase for the treatment of infantile colic. The benefits of lactase remain unproven. Randomized trials of lactase treatment for infantile colic have conflicting results .

Sucrose — We do not suggest sucrose for the treatment of colic. Although oral sucrose appears to reduce some types of pain in neonates, the evidence that it is beneficial in reducing crying in colicky infants is limited.

Infant massage — We do not suggest infant massage for the treatment of infantile colic. A 2010 systematic review found no evidence of benefit and the potential harm of unsettling or overstimulating colicky infants.

Simethicone — We do not suggest simethicone for the treatment of infantile colic. Simethicone is a medication that causes gas bubbles to coalesce, facilitating expulsion. Simethicone is generally considered to be safe, but it may interact with levothyroxine in infants being treated for congenital hypothyroidism resulting in undertreatment.

Herbal remedies — We do not suggest herbal remedies (eg, herbal teas, fennel seed, gripe water [a mixture of herbs and water]) for the treatment of infantile colic. Although a few randomized trials suggest that specific herbal remedies may be beneficial in reducing crying compared with placebo, the benefits are largely unproven. Given the lack of standardization and regulation of herbal products, the benefits do not outweigh the potential risks (eg, contamination with bacteria, toxins, or particulate matter; unlabeled ingredients, such as alcohol). Prolonged ingestion of herbal teas may lead to decreased milk intake.

Homeopathic remedies — We do not suggest homeopathic remedies for the treatment of colic. They have not been proven to be effective.

Homeopathic remedies often are considered nontoxic because of the low concentrations of active ingredients. However, the labels of homeopathic products may not report all of the ingredients, some of which may have toxic effects. As an example, gas chromatography-mass spectrometry analysis of a homeopathic remedy for colic that was associated with an increased risk of apparent life-threatening events found that it contained ethanol, propanol, and pentanol, in addition to three potentially toxic substances that were listed as active ingredients (Citrullus colocynthis [bitter apple], Veratrum album [white hellebore], and Strychnos nux-vomica [strychnine tree]). C. colocynthis is also found in Cocyntal and Hyland colic tablets.

Acupuncture — We do not suggest acupuncture for the treatment of colic. The potential benefits are unproven.

Follow-up — The frequency of follow-up for colicky infants is individualized. Some infants and caregivers may require frequent follow-up (by phone or in person) and re-examination to be reassured that the infant is continuing to do well and growing normally. Other infants whose caregivers are coping well and have strong support networks can be seen less frequently (eg, at regularly scheduled health maintenance visits). In all cases, caregivers should be counseled to return if the infant develops symptoms that were not present during the initial evaluation (eg, vomiting, rash)

INDICATIONS FOR REFERRAL

Most infants with colic can be managed by the primary care provider. Referral to a developmental behavioral pediatrician or mental health provider may be warranted for caregivers who are extremely anxious or in need of additional reassurance.

OUTCOMES

Caregivers of colicky infants experience stress, fatigue, guilt, and depression. Some researchers have postulated that colic may disturb the child-caregiver interaction and thus have long-term effects on the family and child. However, the data on the sequelae of colic are conflicting.

Temperament and behavior — Several studies show that temper tantrums are more common among formerly colicky infants. In two follow-up studies, caregivers of formerly colicky infants reported more frequent temper tantrums at three and four years of age than caregivers of control children. In a meta-analysis of longitudinal studies, the risk of behavior problems in later childhood was increased when colic persisted at five months of age. The risk was greatest when persistent colic was accompanied by other regulatory problems (eg, feeding, sleeping) and psychosocial risk factors, which makes it difficult to establish a causal relationship. However, in a subsequent prospective study, colic that self-resolved before age six months was not associated with difficult temperament or behavior problems at age two to three years.

Caregivers of formerly colicky children perceive their toddlers’ temperaments as more difficult than caregivers of noncolicky children. In a follow-up study, caregivers described their formerly colicky children as more emotional at age four years (eg, “cries easily” or “tends to be somewhat upset”) than noncolicky infants. Caregivers in another one-year follow-up survey also rated their formerly colicky children as more difficult. However, these children did not differ from control children according to the Toddler Temperament Scale. The discrepancy between the caregiver’s perception of the child’s temperament and the child’s actual temperament may reflect the long-term effects of colic on caregiver-child interaction. Another possibility is that factors that predispose an infant to colic also cause problems with caregiver-child interactions.

Sleep patterns — Prospective studies regarding the relationship between colic and the development of childhood sleep problems have conflicting results. The conflicting results may reflect differences in caregiver perception or in caregiver-child interaction for caregivers of children with and without histories of colic.

Family functioning — Studies also differ regarding the effects of colic on family functioning. In a case-control study, family functioning was assessed at one year of age in families of infants with and without colic. Families in the severe colic group had more difficulties in communication, unresolved conflicts, dissatisfaction, and lack of empathy and flexibility. However, other observational studies found no effects of colic on family functioning at two to three years of age. Perhaps the effects of colic on family functioning are present early on but do not persist to three years of age.

Asthma and atopy — Prospective studies evaluating the development of asthma and atopy among infants with colic have conflicting results.

Cognitive development — Colic does not appear to influence long-term cognitive development.