Lactase Enzyme Supplementation for Growth and Feeding Tolerance in Preterm Infants

Lactase Enzyme Supplementation: Efficacy to Promote Growth and Feeding Tolerance in Preterm Infants in Egypt

Preterm infants commonly experience feeding intolerance, which can delay advancement of enteral feeding and impair early growth. This randomized double-blind controlled trial evaluated whether lactase enzyme supplementation could improve feeding tolerance and growth in Egyptian preterm infants born before 34 weeks of gestation. Infants were assigned to receive either feeds supplemented with lactase enzyme or standard feeds without lactase for 2 weeks from the start of enteral feeding. The study hypothesized that lactase supplementation would reduce signs of feeding intolerance and improve weight gain. Outcomes included feeding intolerance symptoms, stool markers of carbohydrate malabsorption, feeding progression, growth parameters, and selected clinical outcomes including necrotizing enterocolitis.

Study Overview

• Status: Completed
• Conditions: Prematurity; Lactose Intolerance; Feeding Intolerance
• Intervention / Treatment: Dietary supplement: Lactase Enzyme Supplementation

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo Governorate
    • Cairo, Cairo Governorate, Egypt, 11511
      • Cairo University Children's Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Preterm infants born before 34 weeks of gestation
• Infants prescribed to start enteral feeding
• Absence of gastrointestinal disorders at enrollment, including necrotizing enterocolitis

Exclusion Criteria:

• Congenital heart disease
• Other serious congenital malformations
• Cow's milk protein allergy symptoms such as abdominal distension or increased exhaust
• Diagnosed necrotizing enterocolitis
• Neonatal sepsis
• Legal guardian unwilling to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lactase Enzyme Supplementation; Preterm infants received enteral feeding with lactase enzyme supplementation for 2 weeks from the start of feeding. For bottle feeds, 1 drop of lactase enzyme was added to every 20 mL of breast milk or formula and incubated for 30 minutes at room temperature before administration. For directly breastfed infants, 5 drops were given before each breastfeed.	Dietary supplement: Lactase Enzyme Supplementation; Lactase enzyme was administered with enteral feeds for 2 weeks from initiation of feeding in preterm infants. For bottle feeds, 1 drop was added to each 20 mL of breast milk or formula and incubated for 30 minutes at room temperature before administration. For directly breastfed infants, 5 drops were given before each breastfeed.
No Intervention: Standard Feeding Control; Preterm infants received breast milk or formula without lactase enzyme supplementation for 2 weeks from initiation of enteral feeding.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight Gain	Mean weight gain rate in grams per day during the 2-week study period.	From initiation of enteral feeding to the end of week 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feeding Intolerance During Week 1	Incidence of feeding intolerance signs during the first week of observation, including gastric residuals, abdominal distension, emesis, and diarrhea.	End of week 1 after initiation of enteral feeding
Feeding Intolerance During Week 2	Incidence of feeding intolerance signs during the second week of observation, including gastric residuals, abdominal distension, emesis, and diarrhea.	End of week 2 after initiation of enteral feeding
Stool Reducing Substances	Presence and degree of reducing substances in stool assessed by Benedict's test as an indicator of carbohydrate malabsorption.	End of week 1 and end of week 2
Stool pH	Fecal pH measured in fresh stool samples as an indicator of carbohydrate malabsorption.	End of week 1 and end of week 2
Feeding Increment	Daily amount of feeding increment achieved during the study period.	Throughout the 2-week observation period
Days to Full Feeding	Number of days required to reach full enteral feeding.	From initiation of enteral feeding until achievement of full enteral feeding, assessed up to 2 weeks
Hospital Stay	Duration of hospital stay in days.	From hospital admission until hospital discharge, assessed up to 3 months

Collaborators and Investigators

• Sponsor: Cairo University

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2022
• Primary Completion (Actual): February 15, 2023
• Study Completion (Actual): February 15, 2023

Study Registration Dates

• First Submitted: March 13, 2026
• First Submitted That Met QC Criteria: March 20, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Enteral feeding; Necrotizing enterocolitis; Preterm infant; Premature infant; Feeding tolerance; Lactase enzyme supplementation; Growth promotion
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Intestinal Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Malabsorption Syndromes; Carbohydrate Metabolism, Inborn Errors; Enterocolitis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Premature Birth; Lactose Intolerance; Enterocolitis, Necrotizing
• Other Study ID Numbers: MD-33-2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the results reported in this study, including demographic characteristics, feeding tolerance assessments, growth parameters, laboratory results, and clinical outcomes, will be made available to qualified researchers upon reasonable request after publication of the main study results. Shared data will exclude direct identifiers and will be released in a de-identified format in accordance with institutional and ethical requirements.
• IPD Sharing Time Frame: Data will be available beginning 6 months after publication of the primary manuscript and for up to 5 years thereafter.
• IPD Sharing Access Criteria: Access will be provided to qualified researchers whose proposed use of the data has been approved by the principal investigator and the relevant institutional authority. Data requestors may be required to submit a methodologically sound proposal and sign a data access or data use agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No