Dodos K, Kalamara TV, Xinias S, Mavroudi A, Kapoukranidou D, Sarantaki A, Diamanti A, Georgakopoulou VE. Effectiveness of the extensively hydrolyzed formulas in the management of infantile colic: A systematic review and meta-analysis. World J Clin Pediatr 2026; 15(1): 111066 [DOI: 10.5409/wjcp.v15.i1.111066]
Corresponding Author of This Article
Vasiliki E Georgakopoulou, MD, Department of Pathophysiology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, 17 Agiou Toma Street, Athens 11527, Greece. vaso_georgakopoulou@hotmail.com
Research Domain of This Article
Pediatrics
Article-Type of This Article
Systematic Reviews
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Mar 9, 2026 (publication date) through Mar 12, 2026
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Journal Information of This Article
Publication Name
World Journal of Clinical Pediatrics
ISSN
2219-2808
Publisher of This Article
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Dodos K, Kalamara TV, Xinias S, Mavroudi A, Kapoukranidou D, Sarantaki A, Diamanti A, Georgakopoulou VE. Effectiveness of the extensively hydrolyzed formulas in the management of infantile colic: A systematic review and meta-analysis. World J Clin Pediatr 2026; 15(1): 111066 [DOI: 10.5409/wjcp.v15.i1.111066]
Konstantinos Dodos, Tsampika-Vasileia Kalamara, Dorothea Kapoukranidou, Laboratory of Physiology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Kentrikí Makedonía, Greece
Stylianos Xinias, Antigoni Mavroudi, 3rd Department of Pediatrics, Aristotle University of Thessaloniki, Thessaloniki 54642, Kentrikí Makedonía, Greece
Antigoni Sarantaki, Athina Diamanti, Department of Midwifery, School of Health and Care Sciences, University of West Attica, Athens 12243, Attikí, Greece
Vasiliki E Georgakopoulou, Department of Pathophysiology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens 11527, Greece
Author contributions: Dodos K and Kalamara TV conceived and designed the study, conducted the literature search, extracted and analyzed the data, and wrote the initial draft of the manuscript; Xinias S and Mavroudi A contributed to the interpretation of clinical findings and provided pediatric expertise; Kapoukranidou D, Sarantaki A, and Diamanti A assisted with literature screening, data organization, and methodological review; Georgakopoulou VE supervised the entire project, provided critical revisions, and ensured the accuracy and integrity of the final manuscript.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Vasiliki E Georgakopoulou, MD, Department of Pathophysiology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, 17 Agiou Toma Street, Athens 11527, Greece. vaso_georgakopoulou@hotmail.com
Received: June 23, 2025 Revised: August 8, 2025 Accepted: October 30, 2025 Published online: March 9, 2026 Processing time: 257 Days and 14.3 Hours
Abstract
BACKGROUND
Infantile colic (IC) is a common, self-limiting condition marked by excessive, unexplained crying. Evidence on the use of extensively hydrolyzed formulas (eHFs) as a dietary intervention remains fragmented.
AIM
To systematically review and meta-analyze the effectiveness of eHFs in managing symptoms of IC.
METHODS
A comprehensive literature search of MEDLINE, Cochrane and Web of Science databases (1980-2025) identified randomized controlled trials and crossover studies assessing the efficacy of eHF in infants diagnosed with IC based on Wessel’s or ROME III criteria. Studies were included if they involved infants ≤ 6 months old on partial or exclusive formula diets, and were excluded if the diagnosis was unclear. Data were synthesized qualitatively and through meta-analysis using odds ratios (OR) and 95% confidence intervals (CI).
RESULTS
Six studies met the inclusion criteria, with a total of 340 infants across intervention and comparator arms. In all studies, eHF significantly reduced crying duration and colic symptoms compared to regular formula or dicyclomine. The meta-analysis showed a pooled OR of 4.8 (95%CI: 2.53-9.11, P < 0.05). Secondary outcomes such as stool consistency and parental quality of life were variably reported but tended to favor eHF.
CONCLUSION
eHF appear significantly more effective than standard formulas and pharmacologic comparators in reducing colic-related symptoms. These findings support eHF as a viable dietary intervention for IC, though larger, well-controlled trials are warranted to confirm long-term outcomes.
Core Tip: Infantile colic is a distressing yet common condition in early infancy. This systematic review and meta-analysis is the first to specifically evaluate the role of extensively hydrolyzed formulas (eHF) in its dietary management. Synthesizing data from six randomized controlled trials, we found that eHF significantly reduces crying duration and improves colic-related symptoms compared to standard formula or pharmacologic interventions. These findings support eHF as an effective and safe dietary option for formula-fed infants with colic, especially in cases where cow's milk protein sensitivity is suspected.
