Morsi WEMA, Eskander AE, Mostafa MG, Ezz ElDin Z, Abdel Maksoud FA, Elrefaee A. Early lactase enzyme supplementation: Efficacy to promote growth and feeding tolerance in preterm infants: A randomized controlled trial. World J Clin Pediatr 2026; 15(4): 124805 [DOI: 10.5409/wjcp.124805]
Corresponding Author of This Article
Amira Elrefaee, MD, Lecturer, Department of Pediatrics, Faculty of Medicine, Cairo University, Al-Manial, Cairo 11956, Al Qāhirah, Egypt. amiraelrefaee@cu.edu.eg
Research Domain of This Article
Nutrition & Dietetics
Article-Type of This Article
research-article
Open-Access Policy of This Article
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/
World J Clin Pediatr. Dec 9, 2026; 15(4): 124805 Published online Dec 9, 2026. doi: 10.5409/wjcp.124805
Early lactase enzyme supplementation: Efficacy to promote growth and feeding tolerance in preterm infants: A randomized controlled trial
Walaa E M A Morsi, Ayman E Eskander, Mohamed G Mostafa, Zahraa Ezz ElDin, Fatma A Abdel Maksoud, Amira Elrefaee
Walaa E M A Morsi, Ayman E Eskander, Zahraa Ezz ElDin, Amira Elrefaee, Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo 11956, Al Qāhirah, Egypt
Mohamed G Mostafa, Pediatric and Neonatology Consultant, Ministry of Health and Population, Cairo 11516, Al Qāhirah, Egypt
Fatma A Abdel Maksoud, Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo 11956, Al Qāhirah, Egypt
Author contributions: Morsi WEMA and Elrefaee A designed the research study; Morsi WEMA, Eskander AE, Mostafa MG, and Ezz ElDin Z performed the research and collected the clinical data; Abdel Maksoud FA performed the laboratory investigations and contributed to data interpretation; Morsi WEMA and Abdel Maksoud FA analyzed the data; Morsi WEMA and Elrefaee A drafted the manuscript; Eskander AE, Mostafa MG, Ezz ElDin Z, and Elrefaee A critically revised the manuscript for important intellectual content; Elrefaee A supervised the study; and all authors read and approved the final version of the manuscript.
AI contribution statement: No artificial intelligence tools were used in the preparation of this manuscript.
Institutional review board statement: The study protocol was approved by the Research Ethics Committee of Cairo University Faculty of Medicine, Cairo, Egypt (approval No. MD-33-2022).
Clinical trial registration statement: This trial was retrospectively registered at ClinicalTrials.gov (Identifier: NCT07494123).
Informed consent statement: Written informed consent was obtained from the legal guardians of all enrolled preterm infants before study participation.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Data sharing statement: The dataset and statistical code are available from the corresponding author upon reasonable request.
Corresponding author: Amira Elrefaee, MD, Lecturer, Department of Pediatrics, Faculty of Medicine, Cairo University, Al-Manial, Cairo 11956, Al Qāhirah, Egypt. amiraelrefaee@cu.edu.eg
Received: June 24, 2026 Revised: August 6, 2026 Accepted: August 26, 2026 Published online: December 9, 2026 Processing time: 87 Days and 8.9 Hours
Abstract
BACKGROUND
Transient lactase deficiency is common in preterm infants, which may contribute to feeding intolerance, poor growth, and adverse clinical outcomes. Early lactase enzyme supplementation can improve the clinical manifestations produced by lactose intolerance in preterm infants with better weight gain and rapid feeding increment.
AIM
To evaluate the efficacy and safety of lactase enzyme supplementation for improving feeding tolerance and promoting growth without adverse outcomes in Egyptian preterm infants.
METHODS
This prospective, randomized, double-blind, controlled trial included a total of 109 preterm infants born before 34 weeks’ gestation; 55 received lactase supplementation and 54 served as controls. Clinical signs of feeding intolerance, growth parameters, stool reducing substances, stool pH, laboratory findings, and other parameters such as hospital stay duration and patient outcome were assessed over 2 weeks.
RESULTS
The intervention group had lower gastric residuals at week 1 (P = 0.0002) and week 2 (P = 0.003), lower abdominal distension at week 1 (P = 0.007) and week 2 (P < 0.001), fewer emesis attacks at week 1 (P = 0.001), and a lower incidence of diarrhea at week 1 (P = 0.004) and week 2 (P = 0.002). Negative stool reducing substances were more frequent in the intervention group at week 1 (P = 0.011) and week 2 (P < 0.001), with significant in-group improvement only in the intervention arm (P < 0.001). Stool pH was higher in the intervention group at week 1 (P < 0.0001) and week 2 (P < 0.0001). Weight gain was greater (P < 0.0001), while necrotizing enterocolitis (NEC) was less frequently reported in the intervention group (P = 0.0448).
CONCLUSION
Lactase supplementation can improve feeding tolerance symptoms, stool pH, and daily weight gain, and may contribute to a reduction in NEC incidence in preterm infants.
Core Tip: This randomized, double-blind controlled trial evaluated lactase enzyme supplementation in preterm infants born before 34 weeks of gestation. Lactase supplementation improved feeding tolerance by reducing gastric residuals, abdominal distension, emesis, and diarrhea. It was also associated with improved stool reducing-substance results, higher fecal pH, and greater daily weight gain. In addition, fewer infants developed necrotizing enterocolitis in the lactase group. These findings suggest that lactase supplementation may be a safe and useful adjunct to enteral feeding in preterm infants.
