We know that there is insufficient research on migraine and migraine treatments. Another problem with migraine research is that many studies are small, with a low number of study participants. It’s difficult to reach firm conclusions from small studies, and the authors who write up these studies often say in their conclusions that more, larger studies are needed on the topics they’re studying. Even when there’s a fairly large study, scientists generally want to see the results replicated in another study.
Meta-analysis (the statistical analysis of a large collection of analysis results from individual studies for the purpose of integrating the findings of multiple studies) is often employed with smaller medical studies to pull together data and identify common results. A research poster and a platform presentation at the American Headache Society’s annual scientific meeting in June (2014), presented the results of meta-analysis of several studies on infant colic and migraine.
Let’s start by defining infant colic. The lay definitions is "Excessive, frequent crying an otherwise healthy and well-fed infant. "Colic occurs in five to nine percent of infants, peaks at six to eight weeks, and usually resolves in three to four months.1
Infantile colic is defined in the appendix of the International Headache Society’s International Classification of Headache Disorders, 3rd edition (ICHD-3), among the episodic syndromes that may be associated with migraine. The primary purpose of the Appendix is to present research criteria for a number of novel entities that have not been sufficiently validated by research conducted so far.3 Here’s the definition from ICHD-3:
**A1.6 Episodic syndromes that may be associated with migraine
A1.6.4 Infantile colic
Excessive, frequent crying in a baby who appears to be otherwise healthy and well fed.
- Recurrent episodes of irritability, fussing or crying from birth to 4 months of age, fulfilling criterion B
- Both of the following:
- episodes last for 3 or more hours per day
- episodes occur on 3 or more days per week for 3 or more weeks
- Not attributed to another disorder.
Infantile colic affects one baby in five, but failure to thrive needs to be excluded. Infants with colic have a higher likelihood of developing 1.1 Migraine without aura or 1.2 Migraine with aura later in life. Mothers with 1. Migraine have been found to be 2.5 times more likely to have infants with colic than mothers without. For fathers with 1. Migraine, the likelihood of an infant with colic was increased two-fold.
The Research Poster:
“To perform a meta-analysis of studies on the relationship between infant colic and migraine.”
“Infant colic is a common and distressing disorder of early infancy. Its etiology is unknown, making treatment challenging. Several articles have suggested a link to migraine.”
- Studies for this meta-analysis were identified by searching PubMED and ScienceDirect, and by hand searching references and conference proceedings. Included American Headache Society conference proceedings from 2010, 2011 and 2012 and International Headache society conference proceedings form 2007, 2009, 2011, and 2013.
- A total of five studies were included in this meta-analysis:
- For the primary analysis, three studies that had been specifically designed to measure the association between colic and migraine were included.
- For the secondary analysis, two studies that were originally designed for another primary research question were included bringing the total number of study participants to 1,984.
- Data were abstracted:
- from the original studies,
- through communication with study authors, or
- both. Two authors independently abstracted data.
- The main outcome was measured by the association between infant colic and migraine.
- Three studies were included in the primary analysis with a total of 891 subjects.
- Five studies were included in the secondary analysis with a total of 1,984 subjects. In the primary analysis, the odds ratio for the association between migraine and infant colic was 6.5 (95% CI 4.6-8.9, p < 0.001) for the fixed effects model and 5.6 (3.3-9.5, p = 0.004) for the random effects model. In a sensitivity analysis wherein the study with the largest effect size was removed, the odds ratio was 3.6 (1.7-7.6, p = 0.001) for both the fixed effects model and random effects model. In the secondary analysis, the cumulative odds ratio was 3.4 (2.7-4.3, p < 0.001) in the fixed effects model and 3.2 (1.4-7.5, p = 0.007) in the random effects model. All of these statistics indicate a strong association between infant colic and migraine.
"In this meta-analysis, migraine was associated with increased odds of infant colic. If infant colic is a migrainous disorder, this would have important implications for treatment. The main limitation of this meta-analysis was the relatively small number of studies included."2
The association between infant colic and migraine appears robust.
The inclusion of infantile colic in ICHD-3 as a “Episodic syndrome that may be associated with migraine” is justified.
Suggested Future Directions:
- a prospective cohort study, using a mobile device for objective crying time measurement
- safe age-appropriate treatment trials may be justified - behavioral interventions, acetaminophen
Additional Information from the Platform Presentation:
Like migraine, the causes of infant colic are still poorly understood. One theory is that colic is related to gastrointestinal distress from feeding problems. However, the researchers pointed out that colic occurs mostly during evening hours, and its being evening-dominated makes it hard to believe that it’s feeding problems. Dr. Gelfand said,
“The causes of infant colic are still not fully understood, and though some believe there is a relationship between colic and gastrointestinal distress, the data are questionable. Because infantile colic can be extremely stressful for parents, it is important to gain a better understanding of the underlying pathology of the condition. Further studies should be conducted to examine this relationship, as this may provide additional information for physicians and parents in the treatment of infants with colic.”
The researchers pointed to these reasons as their rationale for systematic review and quantitative meta-analysis:
- Provide the best estimate of the measure of association between infant colic and migraine: Several studies have reported an association but magnitude of the observed effect size varied
- Help turn the tide on the GI/feeding theory and broaden point of view
- Assist planning of future prospective cohort studies
Summary and comments:
Diagnosing and treating many health issues, including migraine and its possibly related syndromes, is hampered by a lack of knowledge about their pathophysiology and epidemiology. It’s encouraging to see such dedicated researchers continuing to work toward a better understanding of syndromes possibly related to migraine.
The platform presentation and the research poster discussed above give evidence that infant colic may very well be related to migraine. Hopefully, these researchers and others will continue the investigation of colic so that infants and their families can benefit from it.
1 Gelfand, Amy A.; Goadsby, Peter J.; Allen, Elaine. “Infant Colic and Migraine: A Systematic Review and Meta-Analysis.” Platform Presentation. 56th Annual Scientific Meeting; American Headache Society. Los Angeles. June 27, 2014.
2 Gelfand, A.A.; Goadsby, P.J.; Allen, I.E. “Infant Colic and Migraine: A Meta-Analysis.” Poster Presentation. 56th Annual Scientific Meeting; American Headache Society. Los Angeles. June, 2014.
3 Headache Classification Committee of the International Headache Society. "The International Classification of Headache Disorders, 3rd edition (beta version)." Cephalalgia. July 2013 vol. 33 no. 9 629-808 10.1177/0333102413485658
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Teri Robert is a leading patient educator and advocate and the author of Living Well with Migraine Disease and Headaches. A co-founder of the Alliance for Headache Disorders Advocacy and the American Headache and Migraine Association, she received the National Headache Foundation’s Patient Partners Award and a Distinguished Service Award from the American Headache Society. Teri can be found on her website, and blog, Facebook, Twitter, StumbleUpon, Pinterest, LinkedIn, and Google+.