Infantile colic and small intestinal function: a nutritional problem?

Approximately 25% of infants with moderate or severe colic (crying > 3 h d(-1)) have a cow's milk-dependent colic. The author recommends a strict cow's milk-free diet for the mother (with an extra supplement of calcium) in breastfed infants and a casein-hydrolysate formula for formula-fed infants. With this dietary regimen, there will be no nutritional problems. Later in infancy a relatively high proportion of the infants will continue to show an adverse reaction to cow's milk and will also develop allergies to other foods. Several signs (e.g. increased macromolecular absorption, increased motilin levels in serum, increased breath hydrogen excretion, decreased gallbladder contractility) indicate an abnormal intestinal function in colicky infants. The nature of this abnormality is still unknown.     

Infantile colic and small intestinal function: a nutritional problem?

Approximately 25% of infants with moderate or severe colic (crying > 3 h d⁻¹) have a cow's milk-dependent colic. The author recommends a strict cow's milk-free diet for the mother (with an extra supplement of calcium) in breastfed infants and a casein-hydrolysate formula for formula-fed infants. With this dietary regimen, there will be no nutritional problems. Later in infancy a relatively high proportion of the infants will continue to show an adverse reaction to cow's milk and will also develop allergies to other foods. Several signs (e.g. increased macromolecular absorption, increased motilin levels in serum, increased breath hydrogen excretion, decreased gallbladder contractility) indicate an abnormal intestinal function in colicky infants. The nature of this abnormality is still unknown.     

The size and contractility of the gallbladder in infants

The size of the gallbladder and the common bile duct as well as the contractility of the gallbladder were measured in infants under the age of 1 year. A total of 43 healthy infants were studied at their routine visit to the well-baby clinic at the ages of 6 weeks, 4 months, 8 months or 12 months. Gallbladder size was measured before and after a test meal. Fasting gallbladder size increased with the age of the infants. However, when the size was corrected for the infant's weight, no age-related variation was found. The contraction index (CI) was determined as a percentage decrement of planimetric gallbladder size from the initial size. The mean CI declined with age from 75% (±27%) mean (±SD)) at the age of 6 weeks to 24% (±28%) at the age of 12 months. Overall CI varied from –44% to 100%. An increase in gallbladder size after the test meal was observed in 4 infants. Gallbladder volumes were also calculated, but two-dimensional measurements were regarded as more accurate in infants. A large variation was found in the size as well as in the contractility of the gallbladder in infants less than 1 year of age.     

Gallbladder volume and contractility in term and preterm neonates: normal values and clinical applications in ultrasonography

The aim of this study was to establish the normal values and evaluate associated factors of gallbladder volume and contractility in term and preterm neonates by using ultrasonography. Sonographic measurement of gallbladder volume was performed by using the ellipsoid method in 50 preterm and 46 term infants. We collected data soon after delivery and at 6-h fasting, and at 3-h and 6-h fasting following regular milk feeding. Serial postprandial changes of gallbladder volume and contractility were collected at 15-min intervals for one hour. Gallbladder contraction index (C.I.) was determined as percentage decrement of postprandial size from initial size. Fasting gallbladder volume was larger in term group ( p < 0:05). Term neonates more readily showed significant contraction (C.I. > 50%; p < 0:05). In preterm infants significant contraction was clearly observed at postconceptional age > 31 weeks or body weight > 1300 g. The presence of hepatobiliary diseases might be detected by evaluating serial changes of gallbladder volume and contractility under ultrasonography in the neonatal stage.     

Low plasma cholecystokinin levels in colicky infants

OBJECTIVES: Cholecystokinin (CCK) plays an important role in postprandial gallbladder contraction and may also have pacifying behavioral effects, such as inducing satiety and calming in infants. The authors hypothesized that colicky infants have impaired CCK secretion, which contributes to their gallbladder hypocontractility (reported earlier) and excessive crying. METHODS: Cholecystokinin levels of 40 colicky and 37 control infants were evaluated at a mean of age 5 weeks. Plasma CCK levels were drawn before, immediately after, and 1 hour after a regular milk feeding and analyzed using radioimmunoassay (RIA). The contraction of the gallbladder was calculated using ultrasound measurements before and 1 hour after the feeding. The two-tail t test for independent samples was used to test continuous data. RESULTS: The preprandial and 1-hour postprandial plasma levels of CCK were lower in the colicky infants than in the control subjects (P < 0.05). The immediate postprandial CCK levels were also lower in the colicky infants, although this difference did not reach a statistical significance. The proportion of gallbladder contractions did not differ between the study groups. CONCLUSIONS: The authors conclude that low CCK levels in colicky infants may predispose them to excessive crying in the absence of the calming effect of CCK.     

Ghrelin and motilin concentration in colicky infants

Aim: To evaluate serum ghrelin and motilin concentration in infants with infantile colic. Methods: A case-control study was conducted on fasting blood venous samples obtained from 18 infants with infantile colic and 20 healthy infants to measure ghrelin (RIA test) and motilin (RIA test). Results: Colicky infants showed higher ghrelin serum levels (2534.2±600.0 pg/ml; ln 7.8±0.2) than controls (2126.1±281.3 pg/ml; ln 7.6±0.1) (p = 0.011). Serum motilin concentration was significantly higher in colicky infants (94.6±23.2 pmol/l) than in controls (64.1±30.1 pmol/l) (p=0.001). Motilin concentrations were higher in formula-fed colicky infants (104.5±20.4 pmol/l) than in breastfed ones (82.2±21.3 pmol/l) (p = 0.038).

Conclusion: Our finding shows that ghrelin and motilin concentrations are higher in infants with colic than in controls, supporting an organicistic aetiopathogenesis of this disorder. Furthermore, the role of ghrelin on gastrointestinal motility may open new doors to better understand the aetiology of infantile colic.     

Molecular identification of coliform bacteria from colicky breastfed infants

Objective:  To determine the presence of intestinal coliform bacteria in colicky vs healthy infants.
Study design:  We isolated coliform strains from faeces and performed quantitative bacterial cultures in 41 colicky and 39 healthy breastfed infants, identified using PCR with species-specific primers, strain-specific Automated Ribotyping and the API-50E kit for Enterobacteriaceae to identify the most frequent strains.
Results:  Coliform strains were more abundant in colicky infants (median 6.04 log₁₀ CFU/g faeces, range 2.00–8.76) vs controls (median 4.47 log₁₀ CFU/g faeces, range 1.00–8.08) (p = 0.026). Escherichia coli , Klebsiella pneumoniae , K. oxytoca , Enterobacter cloacae , E. aerogenes and Enterococcus faecalis were the predominant species in colicky and healthy infants. The counts of each bacterial species differed between the two groups, and the difference was significant (p = 0.002) for E. coli : median 6.30 log₁₀ CFU/g faeces (range 3.00–8.74) in colicky infants, and median 4.70 log₁₀ CFU/g faeces (range 2.00–5.85) in controls.
Conclusions:  This is the first study to evaluate the colonization patterns of gas-forming coliforms in colicky infants and healthy controls identified by molecular methods. Coliform bacteria, particularly Escherichia coli, were found to be more abundant in colicky infants. Our data could help to shed light on the cause of infantile colic.     

Colicky infants according to maternal reports in telephone interviews and diaries: a large Scandinavian study

In this population-based study the colic incidence was 9.4%, according to telephone interviews with the parents made when the infants were 5 weeks of age (n = 1628), and parental concern about infant crying was common. However, 7-day diaries of colicky and control infants (n = 116 + 119) revealed low distress amounts in colicky infants in general. In the subgroup of Wessel-colicky infants (n = 37), distress episodes were frequent and long lasting, and there was a high proportion of colicky crying versus fussing and normal crying. Even if there may be a reduction in the infantile colic incidence and support for the hypothesis that infantile colic is at least partially "in the eye of the beholder," that is, the concerned parent, a subgroup of infants may be more "genuinely colicky." Women who had stated in late-pregnancy interviews that there is a risk of spoiling an infant with too much physical contact were more likely to have infants with colic, and their infants were more distressed, even when given the same amount of physical contact. This finding warrants further elucidation.     

Breath hydrogen response to milk containing lactose in colicky and noncolicky infants

In 122 healthy newborn infants, we studied the relationship between breath hydrogen (H2) production after feedings containing lactose (human milk or commercial formula) in colicky and noncolicky infants at 6 weeks and 3 months. Eighty-three infants (68%) developed colic (mild, moderate, or severe) by 2.6 +/- 1.8 weeks of age (mean +/- SD). Zero time (baseline) breath H2 values were significantly higher in colicky compared with noncolicky infants at both 6 weeks (40.6 +/- 41.4 vs 14.8 +/- 32.9 ppm) and 3 months (27.7 +/- 38.1 vs 8.5 +/- 18.2 ppm). There were significantly more positive breath H2 tests in colicky compared with noncolicky infants at 6 weeks (78% vs 36%) and 3 months (89% vs 45%). Failure to produce H2 throughout the breath H2 test was significantly more frequent in noncolicky compared with colicky infants at 6 weeks (50% vs 18%) and 3 months (43% vs 4%). These findings remained significant even when infants with mild colic (at 6 weeks and 3 months) were included in the noncolicky group. We conclude that colicky infants produce more breath H2 in the fasting state and in response to feedings containing lactose than noncolicky infants produce. This may represent increased lactose malabsorption, differences in colonic bacterial fermentation conditions, or differences in the handling of colonic gas produced.     

Infant colic syndrome--maternal fantasies of aggression and infanticide

This study examined the impact of infant colic on the emotional state of the mother. Subjects were 23 pairs of mothers and their colicky infants. Structured interviews were conducted with mothers to elicit details around the colic episode and included (1) the emotional state experienced by the mother, (2) the quality and content of the mother's fantasies in response to her infant, and (3) the emotional impact on the parents. Explicit aggressive thoughts and fantasies were revealed by 16 (70%) of the mothers while six (26%) admitted thoughts of infanticide during their infant's colic episodes, a finding notable because previously this has not been documented in medical literature. All mothers experienced physical and psychological symptoms in response to their infant's colic. More than 90% of the mothers with a colicky infant experienced significant marital tension and disruption in their social contacts. The findings suggest that physician receptivity and skill in uncovering the physical and psychological impact of colic on parents is essential for the physical and emotional well-being of the family. Active support and counseling by physicians is critical to diminish any potential for abuse and infanticide in these infants.     

Motilin, Vasoactive Intestinal Peptide and Gastrin in Infantile Colic

ABSTRACT. Intestinal hyperperistalsis is one part of the clinical picture in infantile colic. Three gut hormones involved in the regulation of gut motility; motilin, vasoactive intestinal peptide (VIP) and gastrin, were measured with the RIA method in: 40 infants with infantile colic, (age 2–22 weeks), 42 healthy age-matched infants, 11 children (age 3–36 months) with gastrointestinal disorders, and 20 children (age 3–36 months) with non-gastrointestinal disorder. Basal s-motilin levels were raised in infants with infantile colic ( p <0.01) and in children with other gastrointestinal disorders ( p <0.001). Formula-fed infants had higher basal s-motilin levels than the breast-fed infants ( p <0.05). P-VIP and s-gastrin levels were raised in children with other gastrointestinal disorders ( p <0.05), but not in infantile colic. Formula-fed colicky infants had higher s-gastrin levels than the breast-fed colicky infants ( p <0.05). We suggest that the increased s-motilin level in infantile colic might account in part for the clinical picture of this disorder.     

Bacterial counts of intestinal Lactobacillus species in infants with colic

Intestinal colonization by lactobacilli is suggested to be a prerequisite to normal mucosal immune functions. An inadequate level of lactobacilli may be involved in appearance of allergic disease of which, infantile colic, is often considered an early clinical manifestation. The aim of the study is to evaluate intestinal lactobacilli in breast-fed infants with infantile colic and healthy infants. Fifty-six breast-fed infants, aged 15-60 days were enrolled in the study and divided into two groups: colicky (30 cases) and healthy (26 cases) according to Wessel's criteria. Stool samples were collected, diluted and cultured on selective media. The colonies were counted, reported as colony forming unit (cfu) per gram of faeces and identified by biochemical methods. Different colonization patterns of lactobacilli were found among colicky and healthy infants. Lactobacillus brevis (4.34 x 10(8) cfu/g) and L. lactis lactis (2.51 x 10(7) cfu/g) were found only in colicky infants while L. acidophilus (2.41 x 10(7) cfu/g) was found only in healthy infants. Lactobacillus brevis and L. lactis lactis might be involved in the pathogenesis of infantile colic increasing meteorism and abdominal distension. Further studies are required to understand how the observed differences may be involved in the pathogenesis of this common disorder.     

Motilin, vasoactive intestinal peptide and gastrin in infantile colic

Intestinal hyperperistalsis is one part of the clinical picture in infantile colic. Three gut hormones involved in the regulation of gut motility; motilin, vasoactive intestinal peptide (VIP) and gastrin, were measured with the RIA method in: 40 infants with infantile colic, (age 2-22 weeks), 42 healthy age-matched infants, 11 children (age 3-36 months) with gastrointestinal disorders, and 20 children (age 3-36 months) with non-gastrointestinal disorder. Basal s-motilin levels were raised in infants with infantile colic (p less than 0.01) and in children with other gastrointestinal disorders (p less than 0.001). Formula-fed infants had higher basal s-motilin levels than the breast-fed infants (p less than 0.05). P-VIP and s-gastrin levels were raised in children with other gastro-intestinal disorders (p less than 0.05), but not in infantile colic. Formula-fed colicky infants had higher s-gastrin levels than the breast-fed colicky infants (p less than 0.05). We suggest that the increased s-motilin level in infantile colic might account in part for the clinical picture of this disorder.     

Treatment of infantile colic with surface active substance (simethicone)

The effect of Simethicone on "colicky" (n = 27) infants was tested in a double-blind cross-over study. Three different parameters were used to measure the efficiency of the treatment: interviews, 24-hour records and behavioral observations. No effects of Simethicone on the symptoms of infantile colic could be demonstrated. However, 67% of the infants improved during the treatment, which could be ascribed to a high-grade placebo-effect.     

Cow's milk whey protein elicits symptoms of infantile colic in colicky formula-fed infants: a double-blind crossover study

There are several causes of infantile colic. The aim of this study was to evaluate, under controlled conditions, whether bovine whey proteins can elicit symptoms of infantile colic in colicky formula-fed infants. The mean age for entering the study was 6.4 weeks and the mean age for colic debut was 3.7 weeks. In 24 of 27 infants with severe colic, the symptoms disappeared when they were given a cow's milk-free diet (Nutramigen). These 24 infants were entered into a double-blind crossover study. The infants (receiving cow's milk-free diet) were given the contents of identical capsules with each meal during day 6. The same procedure was repeated on day 10. The capsules contained either whey protein powder (with Nutramigen added) or human albumin powder (with Nutramigen added). Eighteen infants receiving the whey protein-containing capsules reacted with colic, two infants receiving placebo reacted with colic (P less than .001), and four infants did not react at all. Crying hours per day for the 24 infants were 5.6 hours for formula-fed infants and 0.7 hour for cow's milk-free diet-fed infants (P less than .001). Crying hours per day were 3.2 hours for the infants receiving whey protein capsules and 1.0 hour for those receiving placebo (P less than .001). In conclusion, bovine whey protein can elicit symptoms of infantile colic in colicky formula-fed infants.     

Treatment of Infantile Colic with Surface Active Substance (Simethicone)

ABSTRACT. The effect of Simethicone on "colicky" (n=27) infants was tested in a double-blind cross-over study. Three different parameters were used to measure the efficiency of the treatment: interviews, 24-hour records and behavioral observations. No effects of Simethicone on the symptoms of infantile colic could be demonstrated. However, 67 % of the infants improved during the treatment, which could be ascribed to a high-grade placebo-effect.     

5-Hydroxy-3-indole acetic acid levels in infantile colic: Is serotoninergic tonus responsible for this problem?

Abstract Levels of 5-hydroxy-3-indole acetic acid (5-OHIAA), a metabolite of serotonin, were studied in infants with infantile colic in order to investigate the aetiology of infantile colic pathogenesis. The study included 16 patients with infantile colic and 10 control subjects. Random urinary 5-OH IAA levels of colicky infants were found to be higher than those in the control group. This finding suggested that high serotonin levels may be responsible for infantile colic.     

Infantile colic and type of milk feeding

The prevalence of colic with respect to the type of milk feeding in the first 17 weeks of life was assessed by questioning the parents of 964 healthy infants aged 2 to 52 weeks. There was a similar prevalence of colic in infants fed human milk (20%), formula (19%), and formula-supplemented human milk (21%). Intestinal damage, determined by measuring random fecal alpha 1-antitrypsin concentrations in 206 infants aged 2 to 17 weeks and fecal hemoglobin concentrations in 200 of these, was not more likely in infants with colic at the time of study. The occurrence of adverse reactions at the time of introduction of fresh whole cow's milk into the diet of previously colicky infants was uncommon. Our results suggest that dietary protein hypersensitivity is probably not the cause of colic in most healthy young infants.     

The balance of the autonomic nervous system is normal in colicky infants

Excessively crying, hard-to-soothe infants are described as colicky. The self-limiting course of infantile colic during early infancy suggests an etiology of transient developmental dysmaturation. It has been proposed that emotional characteristics such as temperament and self-soothing ability are correlated with the balance of the autonomic nervous system. Heart rate variability (HRV) analysis was used for evaluating the balance of the autonomic nervous system in colicky and control infants during and after the colicky period. HRV analysis was carried out on 12 colicky infants and 14 control infants at the age of 2 mo, and repeated on 10 colicky and 11 normal infants at the age of 7 mo. Measurements were performed during polygraphically confirmed slow-wave sleep (sleep stages 3 and 4). Three HRV frequency bands were defined, including a high (0.2-1.0 Hz), middle (0.12-0.2 Hz) and low (0.025-0.12 Hz) frequency variability. There were no differences between the study groups in any of the three HRV frequency bands analyzed. The high frequency variability increased significantly with age in both study groups (p = 0.009). Conclusion: The findings suggest that imbalance between the parasympathetic and the sympathetic nervous system is not associated with infantile colic and that, in accordance with previous findings, control of HRV shifts in a parasympathetic direction with increasing age during the first year of life.     

Sequelae of infant colic: evidence of transient infant distress and absence of lasting effects on maternal mental health

BACKGROUND: Colic is widely believed to remit by 3 months of age, with little lasting effect on the infant or the family. OBJECTIVES: To determine the prevalence of colic at 3 months and the proportion of cases of colic (identified at 6 weeks) that remitted by 3 months; to identify the factors predictive of colic's remission; and to explore the potential lasting effects of colic on maternal mental health. DESIGN: Prospective cohort study of 856 mother-infant dyads. Self-administered questionnaires were mailed to mothers at 1 and 6 weeks and 3 and 6 months post partum. Standardized instruments were incorporated into the first and last questionnaires to assess maternal anxiety, postnatal depression, and social support. At 6 weeks and at 3 months, mothers completed the Barr diary and/or the Ames Cry Score. RESULTS: Data from 547 dyads were available for analysis. The prevalence of colic at 3 months was 6.4%. More than 85% of cases of colic had remitted by 3 months of age. These infants were more likely to be female, whereas the mothers of these infants were more likely to have received pain relief during labor/delivery and to have been employed during pregnancy. Reductions in scores for trait anxiety and postnatal depression, although smaller for mothers whose infants were colicky at 6 weeks of age, were not significantly different from those of mothers whose infants were never colicky. CONCLUSION: This study provides support for the belief that, in most cases, colic is self-limiting and does not result in lasting effects to maternal mental health.