Rev Assoc Med Bras 2023 (May 19); 69 (5): e20230071 ~ FULL TEXT
Dogan Çagri Tanriverdi, Aysu Yildiz Karaahmet, Fatma Sule Bilgiç
Mehmet Akif Ersoy Gögüs Kalp ve Damar
Cerrahisi Egitim ve Arastirma Hastanesi,
Pediatric Cardiology -
Objective: The aim of this study was to systematically review the colic and sleep outcomes of nonpharmacological intervention in infants with infantile colic and perform a meta-analysis of the available evidence.
Methods: The literature review for this systematic review was conducted between December 2022 and January 2023 using five electronic databases, namely PubMed, CINAHL, Scopus, Web of Science, and ULAKBIM. Published articles were scanned using MeSH-based keywords. Only randomized controlled trials conducted in the past 5 years were included. The data were analyzed using the Review Manager computer program.
Results: This meta-analysis included three studies involving a total of 386 infantile colic infants. After nonpharmacological treatment, it was found that infants with infantile colic reduced crying time (standardized mean difference: 0.61; 95%CI 0.29–0.92; Z=3.79; p=0.00002), improved sleep duration (standardized mean difference: 0.22; 95%CI –0.04 to 0.48; Z=1.64; p=0.10), and decreased crying intensity (mean difference: –17.24; 95%CI –20.11 to 14.37; Z=11.77; p<0.000001).
Conclusion: According to the meta-analysis findings, it was determined that the risk of bias was low in the studies included and that nonpharmacological chiropractic, craniosacral, and acupuncture treatments applied to infantile colic infants in the three included studies reduced crying time and intensity and increased sleep duration.
Keywords: Crying, Chiropractic, Acupuncture therapy
From the Full-Text Article:
Infantile colic (IC) is characterized by excessive crying and restlessness in babies who develop normally from all other directions. [1–3] IC is a common condition that occurs in 25% of infants.  Wessel et al.  were the first to describe the situation with his “rule of three,” that is, the condition in which the infant cries at least 3 times a day for at least 3 days in the previous 3 weeks.
IC adversely affects the comfort and health of both the infants and the parents, and on the contrary, studies are carried out with different therapeutic perspectives because the exact etiology is unknown. In these studies, drug applications and probiotics [6–8] evaluated the efficacy of interventions involving parental behavior and counseling.  In addition, complementary medicine practices, which are rapidly gaining popularity, are also being studied. In these studies, acupuncture , reflexology , physiotherapy, and visceral osteopathy have been studied to treat IC such as vertebral manipulation.  In the literature, the evidence evaluating the effect of nonpharmacological applications on sleep in infants with IC is limited. For this reason, the aim of this study was to systematically review the colic and sleep outcomes of nonpharmacological intervention in infants with IC and to perform a meta-analysis of the available evidence.
In this study, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement  was compiled in the preparation of the systematic review and meta-analysis.
The following criteria (PICOS) were taken into account in the selection of the studies to be included in the study: participant (P): infants with IC. The infants included in the study had the following criteria for inclusion : infants who have cried for at least 3 days for 3 h a day in the past week and  who have no health problems. Intervention (I): nonpharmacological methods. Nonpharmacological methods include the following : chiropractic , craniosacral therapy , acupuncture , yoga , massage , swaddling, and shaking. Comparison (C) : placebo and  routine care. Results (O): sleep duration, crying intensity, and duration. Study design (S): randomized controlled trials and controlled groups were included. Articles that were not IC, but only had gas complaints, pharmacological and pre-probiotic interventions, and evaluated the effect of the interventions other than sleep and IC intensity were excluded from traditional and systematic reviews.
The literature review for this systematic review was conducted between December 2022 and January 2023 using five electronic databases (PubMed, CINAHL, Scopus, Web of Science, and ULAKBIM). The studies in which the efficacy of nonpharmacological interventions in infants with infants with IC were examined by selecting keywords. The keywords were “baby” OR “newborn” OR “infant” AND “therapy” OR “nonpharmacological” OR “alternative therapy” AND “infantile colic” OR “crying” AND “sleep” AND “crying intensity.” The search strategy was changed according to the characteristics of each database. In addition, reviews on articles included in systematic reference lists and other previous systematic reviews were checked to reach further studies.
The data analysis Meta-analysis was performed using Review Manager 5.4 (The Nordic Cochrane Center, Copenhagen, Denmark). The heterogeneity between the studies was evaluated using Cochran's Q test and Higgins’ I˛, and it was accepted that I˛ greater than 50% showed significant heterogeneity. Accordingly, random effect results were taken into account when I˛ was greater than 50%, and fixed effect results were taken into account if it was less than the value. Odds ratio for categorical variables, mean difference (MD), and standardized mean difference (SMD) for continuous variables were calculated. MD or SMD, along with the corresponding 95% confidence interval (CI), is appropriately pooled for continuous variables based on whether the results are measured on the same scales. All tests were calculated from two-pronged tests, and a p-value of less than 0.05 was considered statistically significant. The quality of the articles in randomized controlled trials and the Version 2 of the Cochrane Risk-of-Bias (RoB-2) tool were used for randomized trials.
The PRISMA flowchart is summarized for literature review and selection. A total of 15 studies were reached through electronic database search and manual search. All 15 articles whose full texts could be accessed were examined. Titles and abstracts were read to identify relevant articles; two articles were excluded because of review articles, protocols, replicates, different populations, and not meeting the inclusion criteria. The remaining 13 full texts were evaluated for suitability. Three randomized controlled trial (RCT) articles were included in the quantitative synthesis as they met the required criteria (Table 1). The three RCT articles included outline the study.
This systematic review and meta-analysis included three studies involving a total of 386 IC infants to assess the impact of nonpharmacological interventions on IC intensity and sleep duration outcomes. [10, 14, 15] In the interventions for IC described in the articles included in the study, Holm et al.  applied chiropractic, Castejón et al.  applied craniosacral therapy, and Landgren et al.  applied acupuncture. While the intervention period of the studies in the review lasted 2 weeks, Castejón et al.  evaluated the first day and the first week of the intervention and ended the intervention if the symptoms regressed. In two of the articles, due to the placebo effect, infants in the control group were called to the clinic and stayed with the specialist for 5 min without their parents. [10, 14] In the study by Castejón et al. , the control group was instructed to cope with IC. Nonpharmacological interventions to IC infants in the intervention group, Holm et al.  performed chiropractic twice a week for 2 weeks on IC infants in the intervention group. Castejón et al.  administered 1–3 sessions of craniosacral therapy to infants in the intervention group depending on the reduction of their symptoms. Landgren et al.  performed standard acupuncture at LI4 to a group twice a week for 2 weeks, while one group received traditional acupuncture points at LI4, ST36, or Sifeng, depending on the baby's symptoms, according to the diary. A crying diary and a sleep diary were used in all of the studies, and Castejón et al.  measured IC intensity with the Infant Colic Intensity Questionnaire.
The results of the meta-analysis were presented as Forest Pilot. In the included studies, IC was examined with improvement in crying duration, sleep duration, and crying intensity. The results of the research by Landgren et al.  were sleep duration and crying after the first and second interventions in the beginning. The Infant Pubic Intensity Per Day Questionnaire assessed sleep duration, crying time, sleep time, and being happy while awake before and after all interventions.
In three studies reviewed, the authors reported results on crying duration in the pre- and post-treatment periods. While the mean combined results of the studies did not differ in the post-treatment groups (SMD: 0.61, 95%CI 0.29–0.92, Z=3.79, p=0.00002), the effect of nonpharmacological treatment on crying time showed a significant difference between the groups (Figure 1A). In one study reviewed, the authors reported results on crying intensity in the pre- and post-treatment periods. The combined results of the studies showed that after treatment (MD: –17.24, 95%CI: –20.11 to 14.37, Z=11.77, p<0.000001), the effect of nonpharmacological treatment on crying intensity was significantly different between the groups and its intensity decreased (Figure 1B).
In the two studies examined, the authors reported results regarding sleep duration in the pre- and post-treatment periods. The combined results of the studies showed that while they did not differ in the post-treatment groups (SMD: 0.22, 95%CI: –0.04 to 0.48, Z=1.64, p=0.10), there was a significant difference in the effect of nonpharmacological treatment on sleep duration between the groups (Figure 2).
All the research has identified an adequate method for the random assignment of participants to treatment groups. [10, 14, 15] Therefore, there is a low risk of nepotism error. All studies reported adequate distribution secrecy using sequentially numbered and sealed opaque envelopes and rated them with a low risk of favoritism error. [10, 14, 15] In the two studies included in the meta-analysis, participants and researchers could not go blind to the study, so the two studies assessed participants and staff at risk of nepotism by blinding them, and this was taken into account when interpreting the findings. [14, 15] Three studies assessed data at low risk as a result of blinding. [10, 14, 15] In three studies 10,14,15 , the effect has been so small that it has been balanced or not affected by the intervention and control groups to stop working. For this reason, we concluded that the risk of attrition is low. Because they discussed the significant results reported in all study methods, including negative results, and matched those reported in their records, all studies included in the meta-analysis were considered to have a low risk of reporting bias. For each study included, we described important concerns regarding other possible sources of bias that were not previously addressed in the above categories. [10, 14, 15]
This study aimed to systematically review the colic and sleep outcomes of nonpharmacological intervention in infants with IC and make a meta-analysis of the available evidence. According to the meta-analysis findings, the studies included in the analysis were found to have a low risk of bias, and in all three included studies, nonpharmacological chiropractic, craniosacral, and acupuncture treatments applied to IC infants reduced crying time and intensity and increased sleep duration.
Infants with IC begin to cry at the same time every day, and these cries cannot be stopped. [1, 2] In a meta-analysis study, prebiotic supplementation was reported to be strong in crying intensity of IC infants, while manual therapies were reported to have weak evidence.  In the three studies included in the analysis, crying time was assessed in infants with IC [10, 14, 15] and also evaluated the intensity of crying in a study.  In IC, in addition to the important crying time in infants, the intensity is also important. In this respect, it is thought that there is a weakness in measuring the effectiveness of interventions in two other studies that did not evaluate crying intensity. In addition, in the research, the sleep and crying times of the infants were evaluated by their parents, and they were asked to keep a diary. Parents of infants with IC often have increased levels of anxiety and burnout, and their perception of signs of crying and sleep may be altered.  Research suggests that this evaluation cannot be objective. In addition, two studies included the placebo effect in infants in the control group who were called to the clinic and stayed with the specialist for 5 min without their parents. [10, 14] This suggests that it reduces bias in the evaluation process between groups.
In infants with IC, crying and attacks usually begin in the evening or at midnight and last for at least 3 h. This situation adversely affects the level and quality of sleep for both the baby and the parents. [1, 2] It was found that the nonpharmacological methods used in the studies included in the analysis increased sleep duration. A study reported that IC is reduced in the infants of mothers who massage their infants.  In the three studies included in the analysis, IC asked parents to keep a sleep diary to assess sleep duration. [10, 14, 15] Keeping a stopwatch for the sleep duration of infants is considered quantitative and objective data and can be considered reliable. However, in the studies evaluating sleep in term infants, devices that record the sleep-wake status and duration are used.  A study reported that the majority of mothers used medical and complementary therapies together in the treatment of IC and that the rate of mothers benefiting from complementary therapies was higher than medical treatment.  In line with these findings, nonpharmacological treatments are preferred by the parents of IC infants, and it is seen that there is weak evidence in line with the results of this meta-analysis. In addition, studies examining the effect of interventions on sleep in infants with IC are very limited.
In three studies included in this analysis, chiropractic, craniosacral, and acupuncture treatments for IC infants were found to increase sleep duration while reducing crying duration and intensity. Although there are effective and available methods in IC, the levels of evidence obtained are weak. Randomized, placebo, and double-blind controlled trials with objective assessments such as measurement with more actigraphy to improve sleep in IC infants, which have an important place for infant development, may be recommended.
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