Parenting an infant can be totally overwhelming. One of the earliest challenge many face is learning to deal with periods of intractable crying. I often speak with sleep deprived parents when they’re looking for something — anything — to stop their baby from crying. They’ve typically been told by friends of family that their baby must have “colic” and they’ve come to the pharmacy, looking for a treatment. Colic is common, affecting up to 40% of babies in the few months of life.

While distressing, colic is a diagnosis of exclusion — that it, it is given only after other causes have been ruled out (hunger, pain, fatigue, etc.). The most common definition for colic is fussing or crying for more than 3 hours per day, more than 3 days per week, for more than 3 weeks. These criteria, first proposed by Morris Wessel in 1954, continue to be used today. However, scientific evidence to explain the cause is lacking. Ideas proposed include:

• changes in gastrointestinal bacteria/flora
• food allergies
• lactose intolerance
• excess gas in stomach
• cramping or indigestion
• intolerance to substances in the breast milk
• behavioural issues secondary to parenting factors

Despite its intensity, colic resolves on its own with no interventions. By three months of age, colic has resolved in 60% of infants. By four months, it’s 90%. It sounds harmless and short-lived, but colic’s ability to induce stress in parents cannot be overstated. Parents may be angry, frustrated, depressed, exhausted, or just feel guilty, ascribing their baby’s cries to some parenting fault.

Given our lack of understanding of the true cause of colic, there’s no shortage of cures that have been proposed. From drugs, to supplements, to manual therapies, everyone has their preferred intervention. As a pharmacist, I’m usually asked about drug and non-drug treatments. In particular, I’m often asked about gripe water — a cocktail of different ingredients, involving some combination of herbs, sodium bicarbonate, sugar, and alcohol. Invented by pharmacist William Woodward in the 1800′s, gripe water was originally develop to treat the fevers of malaria. Over time, it was felt to be helpful for babies with colic — though no rigorous evaluation has ever been conducted [PDF].

So what does work for colic? My usual advice to parents starts with reassurance. It’s not bad parenting, and it will pass, given enough time. But the lack of a clear cause and simple solution is not satisfying to many that I speak with. A discussion of stress management, dietary changes, or feeding changes (all usually recommended as first-line approaches) leaves few satisfied. Some are determined to leave the pharmacy with something. “What about this?” they’ll say, gesturing to a product on the shelf. “Will this help?” And that’s when it’s time to distill the evidence. Nicely, we have two new complementary (I don’t mean that in the CAM sense) systematic reviews published in 2011 that, together, cover most of the common treatments. The first review, Infantile colic: A systematic review of medical and conventional therapies by Belinda Hall and associates in Victoria, Australia, looked at “conventional” treatments — drugs, behavioural therapy, and dietary changes. The second, Nutritional Supplements and Other complementary medicines for infantile colic: A systematic review, is from Rachel Perry, Katherine Hunt, and Edzard Ernst. It looked at CAM therapies — supplements, nutritional products, and manual therapies. The two reviews overlapped with respect to nutritional products. Both papers are behind paywalls — I’ll summarize the highlights of both reviews.

The Hall paper was published the Journal of Pediatrics and Child Health earlier this year. A systematic review, it sought to examine all randomized interventions, cohort studies, and quasi-experimental studies for colic. Despite the ubiquity of colic, there have been few proper evaluations done. In a 30-year search of the literature, only 19 published trials were identified: five on drug treatments, ten on nutritional interventions, and four on behavioural interventions. All studies of drug products had significant quality limitations, including a lack of blinding and randomization information, unclear statisitical analyses, and in one case, no comparison of baseline demographics.

• Simethicone is an “anti-foaming” agent believe to help consolidate air bubbles, leading to their expulsion. It’s found in dozens of products. Two trials compared crying duration — neither showed any significant effect. Overall, there’s fairly good evidence to suggest it is ineffective.
• Dicyclomine is an old drug, now used most frequently (with limited success) to treat irritable bowel syndrome. Again, like simethicone, there are two trials, neither of which suggest there’s any meaningful effects. In addition, it has a nasty side effect profile. On balance, the risk-benefit profile suggests it should be avoided.
• Cimetropium is backed by a single study noting a significant decrease in individual colic episodes, but reported side effects of increased drowsiness. That’s not surprising, given it’s a derivative of belladona. Cimetropium does not appear to be available in North America, the UK, or Australia, however. And in the absence of studies reproducing the effects, and a better evaluation of the toxicity, I’d be hesitant to recommend it anyway.

Nutritional interventions suffer from the same methodological limitations as the drug studies. A lack of proper blinding was the most common bias. Other deficiencies included a lack of baseline characteristics, and unclear definitions of colic. Keeping this in mind, the data look somewhat more promising than drugs. There are mixed results with low-allergenic formulas, with some trials showing modest effects, and others showing no improvements. Promising results were found in breastfed infants who were switched to casein hydrosylate formulas, reducing colic from over 7 hrs/day to just under 3 hrs/day. This finding seems consistent with other studies, but comparisons are complicated by different designs and products used. Low-allergen maternal diets have also been associated with improvements in several studies, though they all are subject to bias due to a lack of blinding. Bottom line: promising but unproven. At least these interventions have minimal risk.

What doesn’t work? High-fibre diets had no effect when evaluated. Nor does lactase (Lactaid). Behavioural interventions have not been shown to suggest any meaningful effects. Examples include modified parent-child interaction, contingent music, and that old standby, “car ride simulation”.

“Alternative” Treatments

From a science-based perspective, “alternative” medicine is a misnomer: when clinical evidence emerge to demonstrate unproven therapies are effective, they become accepted as part of medicine. In short, effective treatment is “medicine,” while ineffective or unproven treatments are not medicine. Yet many are used in the absence of evidence, under monikers like “alternative”, “complementary”, and more recently, “integrative”. In the second review, the authors also conducted a systematic review, identifying randomized controlled trials of children diagnosed with colic, and treated with any form complementary or alternative medicine. Trials needed some form of control (placebo, no treatment, etc.) and needed to measure an outcome like severity, quality-of-life, physiologic parameters, or a reduction in the need of medication or other consequence of treatment. Fifteen trials met inclusion criteria — and were too different to permit meta-analysis. About half were deemed to be of good methodologic quality. Few collected or reported safety data: reinforcing the erroneous assumption that that natural products are inherently safe.

Spinal manipulation — Four studies were found, with three showing results that were statistically significant, yet all three positive trials were noted to have multiple methodologic issues (lack of blinding, etc). The highest quality trial was the only double-blind, placebo-controlled study conducted. It showed no effect in outcomes according to parent reports or crying diaries. (As most of you are aware, Simon Singh has made the lack of evidence of chiropractic for colic quite well known.)

A double-blind comparison of Colimil (fennel, lemon balm, and German chamomile) was evaluated to be more effective than placebo. Again, methodologic problems and a lack of duplicative studies makes an evaluation difficult. Another small trial of fennel tea suggested a beneficial effect, too.

I’ve blogged previously how sugar solutions can provide analgesic effects to reduce vaccination distress. They’ve also been evaluated for colic. Like other interventions, some promising results are watered down by methodologic issues.

Is it a lack of beneficial bacteria in the gastrointestinal tract? Probiotic studies have reported positive effects, albiet with quality issues that included a lack of blinding. This paper also looked at nutritional studies, and flagged the same issues that the other review identified.

In a study of massage, both massage and a vibrating bed were reported to have beneficial effects. The improvement over the duration of the trial may have been due simply to the natural course of the condition. A single reflexology trial had problems with entry criteria and so many flaws it was not possible to drawn conclusions beyond the possible beneficial effects of touch alone.

Conclusion

It’s easy to give the TL;DR version of both reviews: Nothing has been convincingly demonstrated to be effective. And that shouldn’t be surprising. Given we don’t know the actual cause of colic (if there even is a single cause), our interventions are simply shots in the dark, meaning there’s little prior probability — and the data that emerge from these isolated trials becomes much less persuasive. With weak study designs, the probability of publication bias, and the lack of confirmatory data for most treatments, we’re left with some promising areas that require further study – and that’s about it.

But we can draw some conclusions of exclusion: There’s little evidence that conventional drug treatments are safe or effective. There’s also no evidence to suggest behavioural interventions, or manual therapies like chiropractic and massage have any effect. Dietary interventions appear to be the most promising type of treatment, followed by sugar solutions, and remotely, herbal products like fennel tea. While there are significant data quality issues with all trials, at least dietary interventions and sugar solutions have little risk. So for parents determined to try something, these interventions seem to offer the best risk/benefit perspective.  But the best, most effective intervention for colic remains the passage of time. Colic will pass. Reassurance is probably the best advice of all.

References

Hall B, Chesters J, & Robinson A (2011). Infantile colic: A systematic review of medical and conventional therapies. Journal of paediatrics and child health PMID: 21470331
Perry R, Hunt K, & Ernst E (2011). Nutritional supplements and other complementary medicines for infantile colic: a systematic review. Pediatrics, 127 (4), 720-33 PMID: 21444591

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