Abstract
Introduction
Colic in infants leads one in six families (17%) with children to consult a health professional. One systematic review of 15 community-based studies found a wide variation in prevalence, which depended on study design and method of recording.
Methods and outcomes
We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of treatments for colic in infants? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2014 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).
Results
At this update, searching of electronic databases retrieved 47 studies. After deduplication and removal of conference abstracts, 22 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 10 studies and the further review of 12 full publications. Of the 12 full articles evaluated, three systematic reviews and four RCTs were added at this update. We performed a GRADE evaluation for six PICO combinations.
Conclusions
In this systematic overview, we categorise the efficacy for seven interventions based on information relating to the effectiveness and safety of casein hydrolysate milk, cranial osteopathy, Lactobacillus reuteri (probiotic), low-lactose milk, soya-based infant feeds, spinal manipulation, and whey hydrolysate milk.
Key Points
Colic in infants is defined as excessive crying in an otherwise healthy and thriving baby. The crying typically starts in the first few weeks of life and usually resolves within 6 months.
It leads one in six families with children to consult a health professional.
We found insufficient RCT evidence to judge whether replacing cow's milk or breast milk with casein hydrolysate milk, low-lactose milk, soya-based infant feeds, or whey hydrolysate formula is effective in reducing crying time.
Breastfeeding mothers should generally be encouraged to continue breastfeeding.
Soya milk is associated with possible long-term harmful effects on reproductive health.
We found no direct evidence from RCTs about the effects of cranial osteopathy in infants with colic.
Spinal manipulation does not appear to reduce the duration of crying associated with infantile colic, nor does it appear to facilitate recovery.
We found insufficient evidence from high-quality RCTs to determine whether Lactobacillus reuteri (probiotic) is effective at reducing crying time in infants with colic.
Clinical context
General background
Colic in infants is a relatively prevalent condition, causing a lot of distress and uncertainty in parents. As a consequence, many parents will seek professional help.
Focus of the review
To provide professionals with an overview of effective evidence-based treatments for colic and, if possible, provide data on adverse effects of treatments.
Comments on evidence
Many RCTs focus on diets or dietary supplements and different kinds of manipulation. Considerable uncertainty exists regarding the conclusions of many of these studies because of small sample size and low overall quality.
Search and appraisal summary
The update literature search for this overview was carried out from the date of the last search, September 2009, to February 2014. A search back-dated to 1966 was performed for the new options added to the scope at this update. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the overview, please see the Methods section. Searching of electronic databases retrieved 47 studies. After deduplication and removal of conference abstracts, 22 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 10 studies and the further review of 12 full publications. Of the 12 full articles evaluated, three systematic reviews and four RCTs were added at this update.
Additional information
The effectiveness of specific interventions is uncertain. Healthcare professionals may, therefore, wish to consider non-specific interventions first, such as: listening carefully to parents, examining the infant mindfully, trying to reach common ground with the parents, increasing parent confidence and care-skills, and providing opportunities for follow-up visits.
About this condition
Definition
Colic in infants is defined as excessive crying in an otherwise healthy and thriving baby. The crying typically starts in the first few weeks of life and usually resolves within 6 months. Excessive crying is defined as crying that lasts at least 3 hours a day, for 3 days a week, for at least 3 weeks. Because of the natural course of infant colic, it can be difficult to interpret trials that do not include a placebo or have no treatment group for comparison.
Incidence/ Prevalence
Infant colic leads one in six families (17%) with children to consult a health professional. One systematic review of 15 community-based studies found a wide variation in prevalence, which depended on study design and method of recording. Two prospective studies identified by the review yielded prevalence rates of 5% and 19%. One prospective study (89 breast- and formula-fed infants) found that, at 2 weeks of age, the prevalence of crying over 3 hours a day was 43% among formula-fed infants and 16% among breastfed infants. The prevalence at 6 weeks was 12% among formula-fed infants and 31% among breastfed infants.
Aetiology/ Risk factors
The cause is unclear and, despite its name, infant colic may not have an abdominal cause. It may reflect part of the normal distribution of infantile crying. Other possible explanations are painful intestinal contractions, or parental misinterpretation of normal crying.
Prognosis
Infant colic improves with time. For most infants, crying and irritability begin to decrease by 4 months of age.
Aims of intervention
To reduce infant crying and distress, and the anxiety of the family, with minimal adverse effects of treatment.
Outcomes
Presence and duration of colic, as determined by frequency and duration of crying, measured on dichotomous, ordinal, or continuous scales or by parents' perceptions of severity and duration of colic recorded in a diary; adverse effects.
Methods
Search strategy BMJ Clinical Evidence search and appraisal February 2014. Databases used to identify studies for this systematic review include: Medline 1966 to February 2014, Embase 1980 to February 2014, The Cochrane Database of Systematic Reviews 2014, issue 2 (1966 to date of issue), the Database of Abstracts of Reviews of Effects (DARE), and the Health Technology Assessment (HTA) database. Inclusion criteria Study design criteria for inclusion in this review were systematic reviews and RCTs published in English, at least single-blinded, and containing at least 20 individuals (at least 10 in each arm), of whom at least 80% were followed up. There was no minimum length of follow-up. We excluded all studies described as 'open', 'open-label', or not blinded unless blinding was impossible. BMJ Clinical Evidence does not necessarily report every study found (e.g., every systematic review). Rather, we report the most recent, relevant and comprehensive studies identified through an agreed process involving our evidence team, editorial team, and expert contributors. Evidence evaluation A systematic literature search was conducted by our evidence team, who then assessed titles and abstracts, and finally selected articles for full text appraisal against inclusion and exclusion criteria agreed a priori with our expert contributors. In consultation with the expert contributors, studies were selected for inclusion and all data relevant to this overview extracted into the benefits and harms section of the overview. In addition, information that did not meet our predefined criteria for inclusion in the benefits and harms section, may have been reported in the 'Further information on studies' or 'Comment' section. Adverse effects All serious adverse effects, or those adverse effects reported as statistically significant, were included in the harms section of the overview. Pre-specified adverse effects identified as being clinically important were also reported, even if the results were not statistically significant. Although BMJ Clinical Evidence presents data on selected adverse effects reported in included studies, it is not meant to be, and cannot be, a comprehensive list of all adverse effects, contraindications, or interactions of included drugs or interventions. A reliable national or local drug database must be consulted for this information. Comment and Clinical guide sections In the Comment section of each intervention, our expert contributors may have provided additional comment and analysis of the evidence, which may include additional studies (over and above those identified via our systematic search) by way of background data or supporting information. As BMJ Clinical Evidence does not systematically search for studies reported in the Comment section, we cannot guarantee the completeness of the studies listed there or the robustness of methods. Our expert contributors add clinical context and interpretation to the Clinical guide sections where appropriate. Data and quality To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). BMJ Clinical Evidence does not report all methodological details of included studies. Rather, it reports by exception any methodological issue or more general issue that may affect the weight a reader may put on an individual study, or the generalisability of the result. These issues may be reflected in the overall GRADE analysis. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table.
GRADE Evaluation of interventions for Colic in infants.
| Important outcomes | Duration of crying, Presence of colic | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of treatments for colic in infants? | |||||||||
| 2 (192) | Duration of crying | Casein hydrolysate milk (including hypoallergenic diet for breastfeeding mothers) versus standard care (breast milk, cow's milk formula) | 4 | –3 | 0 | –1 | +1 | Very low | Quality points deducted for sparse data, weak methods, and incomplete reporting of data; directness point deducted for inclusion of different interventions; effect size point added for OR >2 |
| 1 (53) | Duration of crying | Low-lactose (lactase-treated) milk (including low-lactose breast milk) versus standard care (breast milk, cow's milk formula) | 4 | –2 | 0 | –1 | 0 | Very low | Quality points deducted for sparse data and methodological flaws; directness point deducted for uncertain lactose intolerance in babies |
| 2 (124) | Duration of crying | Spinal manipulation versus no treatment or sham treatment/holding | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for sparse data; consistency point deducted for significant heterogeneity |
| 2 (155) | Presence of colic | Spinal manipulation versus no treatment or sham treatment/holding | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for sparse data; consistency point deducted for significant heterogeneity |
| 1 (43) | Duration of crying | Whey hydrolysate milk versus standard care (breast milk, cow's milk formula) | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and flawed blinding |
| 2 (126) | Duration of crying | Lactobacillus reuteri (probiotic) versus placebo | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data and randomisation/blinding flaws in 1 study, and markedly different baseline characteristics in the other |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.
Glossary
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Very low-quality evidence
Any estimate of effect is very uncertain.
- Wessel's criteria
Crying for 3 hours or more on at least 3 days in at least 3 weeks.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
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