LOS ANGELES — There is growing evidence that infant colic is a type of migraine headache.

The results of a new meta-analysis linking the 2 conditions suggest that "colic is an age-sensitive phenotype of migraine," according to lead researcher Amy Gelfand, MD, assistant professor, Clinical Neurology and Pediatrics, University of California, San Francisco, and child neurologist, University of California, San Francisco, Headache Center.

Dr. Gelfand believes it may be time to bring colic into the main body of the International Classification of Headache Disorders (ICHD) document from the appendix, where it's now an "episodic syndrome that may be associated with migraine."

Getting a better handle on the association between infant colic and migraine could help put to rest the oft-repeated theory that colic has something to do with feeding and gastrointestinal disorders, said Dr. Gelfand.

Dr. Amy Gelfand

She presented results of the new meta-analysis here at the American Headache Society (AHS) 56th Annual Scientific Meeting.

Fussing, Crying

According to the ICHD-III, colic refers to recurrent episodes of irritability, fussing, or crying. Episodes must last for 3 or more hours a day and occur on 3 or more days a week for 3 or more weeks. Colic peaks at 6 to 8 weeks of age and typically resolves by 4 months of age. The prevalence of colic is between 5% and 19%.

Researchers searched 2 electronic databases (PubMed and ScienceDirect), as well as recent AHS and International Headache Society conference proceedings, for relevant studies.

The primary analysis included studies that examined the association between infant colic and migraine. For a secondary analysis, researchers also included studies that collected data on infant colic and migraine but had a different primary research question.

The primary analysis included 3 studies with a total of 891 participants. One of these studies was conducted by Dr. Gelfand and colleagues. In it, the researchers analyzed 154 surveys and found that infants whose moms had migraine were 2.6 times more likely to have colic.

Another study found that children or adolescents with migraine were 6.6 times more likely to have had infantile colic than those without migraine; a third article included 58 participants and uncovered a similar link.

In a pooled random effects model (which Dr. Gelfand said is "more conservative" than the pooled fixed effects model), the odds ratio (OR) for the relationship was 5.6 (95% confidence interval [CI], 3.3 - 9.5; P = .004).

For the secondary analysis, researchers added 2 more studies, bringing the total number of participants to 1984. Here, the pooled random effects model had an OR of 3.2 (95% CI, 1.4 - 7.5; P = .007).

A sensitivity analysis that removed the largest study did not meaningfully change the results for the primary and secondary analysis or for both the fixed and random effects models, said Dr. Gelfand.

"It appears that the association between infant colic and migraine is quite robust," she noted.

"I think it's justified that infant colic is in the ICHD-III in the section on episodic syndromes that might be associated with migraine, but in the next iteration, it would make sense to pull it from the appendix section and [put it] into the main document," she added.

Infant colic can be extremely stressful for parents. According to research cited by Dr. Gelfand, 2.2% of parents with 1-month-old babies admitted shaking, slapping, or smothering their child to try to stop the crying. By age 6 months, 5.6% of parents have tried one of these "dangerous techniques."

"I don't think that 5.6% of parents are horrible people; it just says that parents are human and by the time their baby is 6 weeks old, they are really tired," and feel at the end of their rope, said Dr. Gelfand.

Cause Unknown

Nobody knows what causes colic, although people have looked at gastrointestinal pathology for clues. However, it is unlikely that colic is caused by intestinal gas.

Dr. Gelfand cited a randomized controlled trial of simethicone (an antifoaming agent sold over the counter to treat gas and bloating) versus placebo that showed no difference in effect.

Furthermore, colic is also not likely a result of feeding methods. Research shows that breast-milk vs formula makes no difference in colic rates. There is also no evidence of lactose intolerance in colicky babies, although an allergy to cow's milk protein may play a role in a subset of infants, said Dr. Gelfand.

She pointed to a recent randomized controlled trial that showed no benefit of probiotics for colicky babies. In fact, some formula-fed infants who were given the probiotic cried or fussed 78 minutes more per day than those who received the placebo (P = .005), she said.

Asked by Vincent Martin, MD, codirector, University of Cincinnati Headache and Facial Pain Program, Ohio, whether autonomic mechanisms could be at play, as these tend to kick in at night, when infants are most colicky, Dr. Gelfand clarified that colic typically occurs in the evening hours, from about 5 to 11 pm, rather than "the wee hours of the morning."

"The way I tend to think of it, is that after they have accumulated a lot of stimulation over the course of the day, babies just need to wind down and let it all go, but there could be some circadian variability."

Although the new meta-analysis included a relatively small number of studies, the overall number of subjects was large (almost 900 for the primary analysis and almost 2000 for secondary analysis).

This research is worthwhile, "given that the tummy way of looking at the problem has failed miserably, and given that shaken baby syndrome is an incredibly serious issue," commented Peter Goadsby, MD, PhD, director, Headache Center, University of California, San Francisco, who was involved in the study.

"It seems to me that shedding new light and getting people to think about this very serious problem in a totally different way is very important."

A prospective cohort study that uses some kind of mobile device to objectively measure crying time without relying on parental input could help objectively determine which babies develop colic and then, over time, which will develop migraine.

"It would be an expensive undertaking and would take lot of patience, but it would be a treasure trove of natural history data about what migraine looks like in the developing brain," said Dr. Gelfand.

Modern technology that can design an instrument that counts footsteps should be able to come up with such a device, perhaps an alarm attached to the baby's foot, said Dr. Gelfand.

In the meantime, parents should be advised to pursue safe and relatively inexpensive means of trying to quiet their baby, including giving acetaminophen, removing stimulation, and holding him or her.

"Holding the baby doesn't require [US Food and Drug Administration] approval, and acetaminophen is a regular sort of medicine," said Dr. Goadsby. "So you can start to look at simple, cheap, globally useful things that could be done everywhere tomorrow. If that reduces even by a small amount the number of kids who have a problem like this, I'm happy with that."

The investigators have disclosed no relevant financial relationships.

American Headache Society (AHS) 56th Annual Scientific Meeting. Presented June 27, 2014.