Literature Review: The Relationship Between Infantile Colic and Cow’s Milk
Aubrey Mahall
Meredith College MS Nutrition
March 21, 2013

The Relationship Between Infantile Colic and Cow’s Milk
Introduction
Infantile colic is a common and taxing syndrome in infants during the first few months of life.
Colic is characterized by unexplained excessive crying, disturbed sleep, hiccupping, severe gas, and abdominal pain 1,2,3 . This disorder is common in both exclusively-breastfed and formula-fed infants, with the approximate prevalence at 20%. Some studies suggest that incidence is age-dependent: with 31% at 2 weeks of age and 12% at 6 weeks among formula-fed infants; but 21% at 2 weeks and
31% at 6 weeks for breastfed infants 1 . The cause has remained unclear. Some of the potential causes include too much food, too little food, wrong feeding technique, increased gas formation in the gut, food intolerance, disturbed mother-child relationship, and neurolability in the infant 4 . This literature review is focused specifically on the dietary relationship with colic. Formula-fed infants may be introduced to colic earlier through direct consumption of cow’s milk, whereas exclusivelybreastfed infants may experience colic slightly later due to cow’s milk proteins transferred via breast milk from mother to infant 2 . This is hypothesized to affect the infant later due to lower concentration exposure when compared to higher concentration exposure in formula-fed infants 2 .
This review is aimed to evaluate the relationship between colic and the specific proteins that may be contributing to infant symptoms. Further, this review strives to determine the implications for registered dietitians and mothers of infants with colic.
Harmful Proteins: Whey and Bovine IgG
There is no clear answer as to which protein or component in cow’s milk is contributing to the symptoms of infantile colic. However, the two major proteins that seem to negatively effect infants are whey and bovine IgG. In two different studies conducted by Lasse Lothe, research revealed that cow’s milk whey can elicit symptoms of infantile colic in certain infants 4 . The purpose of the first study was to determine how often infantile colic was cause by cow’s milk whey protein. Seven years later, the research progressed to study whether bovine IgG proteins could elicit symptoms of infantile colic in colicky formula-fed infants 5 . Both studies were double-blind crossover designs, which strengthen the internal validities of the research.

In the research conducted in 1982, colicky infants that were recruited for the sample were given cow’s milk formula for one week, and soymilk formula for the second week. When infants transitioned to soymilk from cow’s milk, there was a significant decrease in colic-like symptoms 4 .
After symptoms were alleviated, infants were challenged to reintroduction of cow milk through a mixture with soy formula. This integration of the two formulas resulted in detrimental effects on the infant, specifically through the increase of crying symptoms by 53%, when compared to crying symptoms on the exclusive soymilk formula. Their research here suggested that reintroduction of cow’s milk whey protein results in recurrence of symptoms, and should not be added to potential antigenic soy protein 4 . Research conducted seven years later by Lothe used the same methods to discover the impact of bovine IgG proteins on colic. Similarly, data revealed that infants with increased exposure to bovine IgG proteins had upwards of 3.2 hours crying per day when compared to 1.0 hours of crying per day in placebo group infants 5 .
The methodology in the Lothe studies had strengths and limitations to external validity. Both were strengthened by the strict modification of the infants diet through concise formula composition administered by the research team. The initial study had a sample size of 65, whereas the later study only had a sample of size 27. While both yielded small sample sizes, the results from a sample of 65 may be closer in generalizability when compared to the smaller sample. The limitations included observations in the home and short exposure time to the different formulas. While the research team administered the formulas with strict instruction to mother’s, the observation of symptom change was recorded in-home instead of in-lab. Therefore, the research relied solely on parent observation, which could have been inaccurate or misrepresented. And finally, the results in both studies were reliant upon each infant being exposed to the formulas for only one week at a time before switching to a different formula. Results could have been different had the infants ingested each formula for longer periods of time.
Research conducted after these studies, by Clyne and Kulczycki, confirmed findings of the harmful implications of bovine IgG proteins for colicky babies. In a stronger sample size that included
97 mothers, breast milk samples were taken and analyzed for bovine IgG using solid-phase RIA. The results observed that the highest concentrations of 8.5 micrograms/mL were in mothers with infants that had the most severe cases of colic 3 . Cow’s milk infant formulas can contain upwards of 6.4

micrograms/mL of bovine IgG. This data suggests that the more bovine IgG protein an infant is ingesting, the more intense their symptoms of colic will be. This study had great strength behind the fact that data was taken from internal sources, instead of relying on external observations. Acquiring multiple samples of breast milk from multiple mothers was helpful to determine the variability of bovine IgG concentration and its impact on infants with colic. Quantitative research here solidifies the qualitative research that was used in the previous studies conducted by Lothe.
Helpful Proteins: Soy and Casein
Initial research had the purpose of trying to discover which cow’s milk protein was harmful to infants dealing with colic. Unintentionally, the results were able to suggest which proteins may be beneficial for colicky infants 3,4,5 . Future research was molded around the implications that soy and casein concentrated formulas would have beneficial impacts on the symptoms of colic in infants. The previously discussed study of bovine IgG concentrations in cow and mother’s milk also tested the prevalence of bovine IgG in commercially available soy-based and hydrolyzed casein-based formulas.
As expected, the soy and casein formulas had no detectable levels on bovine IgG 3 . This informed future research to concentrate on soy and casein alternatives for cow’s milk intolerant infants.
With this new knowledge, a double blind, multiple-crossover study conducted by Forsyth examined the impact changing formulas between cow’s milk and casein hydrolysate. Included in the study were 17 infants who experienced greater than 3 hours of crying per day due to apparent gastrointestinal distress. Infants were fed either Nutramigen, the casein based formula, or a formula of one-third cow’s milk, two-thirds Nutramigen, in alternating 4 day periods for four study periods.
Similar to the Lothe studies, data was purely qualitative from parent observation diaries. However, this study included a two-day washout period between the formula changes, to ensure complete removal of any protein antigens. Concluded here was marked day-to-day variability in crying behavior, which was independent of the type of formula 6 . There were statistically significant changes from cow’s milk to Nutramigen during the first period, but those results lessened by the third formula change. Here the author concludes casein hydrolysate formula as a beneficial solution only in short-term treatment.

This data is similar to Lothe with the implications of the soy-based formula ProSobee. On the
ProSobee formula 11 infants out of 27 had their symptoms disappear within 48 hours 4 . However, later in the study when the ProSobee was combined with cow’s milk the symptoms reappeared at an even worse degree. The similar conclusion here is that soy-based formula is helpful for short-term lessening of colic symptoms. Authors also suggest that soy protein is antigenic when combined with cow’s whey protein, so the combination is not a suitable substitute 4 . These studies are both limited by sample size, time frame, and parent observation. While Forsyth included 4-day studies with 2-day washout periods, the time frame might remain too short. Further, the conclusions in both are representative of positive short-term changes, but cannot deduce implications for long-term effects.
Implications: Avoidance vs. Counseling
Due to the overwhelming evidence that high concentrations of cow’s milk whey protein and bovine IgG add to the symptoms of colic in infants, the major suggestion is for mother’s to exclusively breastfeed their infants and maintain strict avoidance of cow’s milk in their own diets 2,3,5,6 . But there is still evidence that can only conclude short-term beneficial changes through alternative milk sources 4,6 , so there exists research that suggests parental counseling has greater benefit to families of colicky babies 7 .
In an intervention lasting only one week, mother’s who strictly avoided cow’s milk in their diet had their infants show improvement by an average of 31% less crying and fussing per day 2 . This significant difference was found in cry and fuss time between first and last two days of the intervention. Here, not only were mothers logging their diets; they were also required to chart infant behavior each day on a 15 minute segmented timeline. This strengthened the study by ensuring that documentation had greater accurarcy throughout the entire study period by making intervals so short. In comparison to all treatment conclusions, the improvement rate remains at only 31%, suggesting this too as a short-term solution.
When evaluating counseling interventions in comparison to maternal avoidance diets, the implications may have greater long-term effects. Bruce Taubman, MD, investigated the relationship between not only changing the mother’s diet to cow’s milk avoidance, but also adding instruction to parents on how to respond to their infant’s crying 7 . After a 9 day intervention, groups who were

counseled through reactions to their infants fussing and crying had significantly decreased average crying time when compared to a control group of no counseling. Comparable to most infant crying measures, the parents were required to monitor the changes themselves. In this study, however, the reports were handed in daily and participants discussed and confirmed observations through telephone interviews. This method seems to be stronger because it requires parents to reflect on their observations and re-analyze their descriptions given.
Conclusion:
My evaluation of this material is that infantile colic is a common, short-lived syndrome that occurs most frequently in infants less than 3 months old. There is a large body of research that supports the negative effects of multiple proteins within cow’s milk that contribute to the ill-defined syndrome. Those proteins that have been determined beneficial, soy and hydrolyzed casein, are only supportive of short-term treatments. Solutions to colic are generally: let it run its natural course since it is short-lived, change to non-cow’s milk formulas, or have the mother strictly avoid cow’s milk in her diet and exclusively breastfeed. As there is not one mold to stick to here, my suggestion from this body of research would be for mothers of colicky infants to first seek counseling in order to understand how to better respond to their infants cries. When the infant begins to experience severe colic symptoms I would advocate eliminating cow’s milk from the mother’s diet and exclusively breast feeding since bovine IgG proteins are prevalent in high quantities in commercial cow’s milk formulas and diets of mothers consuming cow’s milk. All in all, while the excessive fussing and crying is distressing to both infant and mother, the research suggests several short-term changes that may help with the disappearance of the syndrome. This information has huge implications for registered dietitians with clients who have colicky infants.

References:
1.
Lucas A, St James-Roberts I. Crying, fussing and colic behaviour in breast- and bottle-fed infants. Early
Human Dev. 1998; 53(1): 9-18.
2.
Rezaei O, Shahzamanian S, Gorgani S, Sajedi F. Temporary Strict Maternal Avoidance of Cow’s Milk and
Infantile Colic. Acta Medica Iranica. 2009; 47(6): 1-4.
3.
Clyne P, Kulczycki A. Human Breast Milk Contain Bovine IgG. Relationship to Infant Colic? Pediatrics.
April 1991; 87(4): 439-444.
4.
Lothe L, Lindberg T, Jakobsson I. Cow’s Milk Formula as a Cause of Infantile Colic: A Double-Blind
Study. Pediatrics. July 1982; 70(1): 7-10.
5.
Lothe, L, Lindberg T. Cow’s Milk Whey Protein Elicits Symptoms of Infantile Colic in Colickly Formula-
Fed Infants: A Double-Blind Crossover Study. Pediatrics. February 1989; 83(2): 262-266.
6.
Forsyth BW. Colic and the effect of changing formulas: a double-blind, multiple-crossover study. J
Pediatrics. 1989; 115: 521-526.
7.
Taubman B. Parental Counseling Compared With Elimination of Cow’s Milk or Soy Milk Protein for the
Treatment of Infant Colic Syndrome: A Randomized Trial. Pediatrics. June 1988; 81(6): 756-761.