The Effect of Lactase-Treated Feeds on Feeding Intolerance in Preterm Infants

This is a randomized, controlled, parallel-group interventional study designed to evaluate the effect of lactase-treated feeds on feeding intolerance in preterm neonates.

Preterm neonates are at increased risk of feeding intolerance because of gastrointestinal immaturity, delayed gastric emptying, immature intestinal motility, and incomplete development of digestive enzyme activity. Lactase activity may be relatively low in preterm infants, potentially resulting in incomplete lactose digestion and contributing to gastrointestinal symptoms associated with feeding intolerance.

Eligible preterm neonates will be enrolled according to predefined inclusion and exclusion criteria. Participants will be randomly allocated into two groups. The intervention group will receive milk feeds treated with lactase enzyme, while the control group will receive milk feeds treated with placebo. The placebo will consist of distilled water administered in an equivalent manner to the lactase preparation.

The study will evaluate feeding tolerance throughout the study period. Clinical parameters related to feeding tolerance will be recorded, including the occurrence and severity of feeding intolerance manifestations and the progression of enteral feeding. Nutritional and growth-related parameters will also be assessed according to the study protocol.

The primary objective is to determine whether lactase-treated feeds improve feeding tolerance in preterm neonates compared with placebo-treated feeds. Secondary objectives include evaluating the effect of lactase supplementation on the progression of enteral feeding and selected nutritional and growth outcomes.

The study is expected to provide evidence regarding whether exogenous lactase supplementation may be beneficial in preterm neonates experiencing feeding intolerance

• Lactase enzyme (Drug): Lactase enzyme treated feeds
• Distilled water (Other): Distilled water administered as placebo to the control group during enteral feeding.

Primary outcomes

• Mean change from baseline in gastric residual volume [From start of intervention till 2 weeks]: Gastric residual volume measured in milliliters before feeding and serially during the intervention period. The outcome will be assessed by comparing the change in gastric residual volume from baseline between the lactase-treated feed group and the placebo group.
• Number of participants with abdominal distension [From initiation of intervention to 2weeks]: Abdominal distension assessed clinically by serial abdominal examination and abdominal circumference measurement during the intervention period. Participants with clinically evident abdominal distension will be recorded.
• Number of participants with vomiting [From initiation of intervention to 2 weeks]: Vomiting episodes will be assessed by clinical observation during the intervention period and recorded for each participant.
• Number of participants with diarrhea [From initiation of intervention to 2 weeks]: Diarrhea will be assessed clinically according to stool frequency and consistency during the intervention period and recorded for each participant.

Secondary outcomes

• Mean change from baseline in body length [From initiation of the study intervention till 2 weeks]: Body length measured in centimeters using a standardized infant length board. Length will be assessed at baseline and at the end of the intervention period.
• Mean change from baseline in body weight [From initiation of intervention to 2 weeks]: Body weight measured in grams using a calibrated neonatal weighing scale. Weight will be measured serially during the study period and the change from baseline will be compared between the lactase-treated feed group and the placebo group.
• Mean change from baseline in head circumference [From initiation of intervention to 2 weeks]: Head circumference measured in centimeters using a non-stretchable measuring tape placed around the largest occipital-frontal circumference. Measurements will be obtained at baseline and at the end of the intervention period.
• Mean change from baseline in mid-upper arm circumference [From initiation of intervention to 2 weeks]: Mid-upper arm circumference measured in centimeters using a non-stretchable measuring tape at the midpoint of the upper arm. Measurements will be obtained at baseline and at the end of the intervention period.

Sex: All, ages: 0 Days to 28 Days

Inclusion Criteria

* Gestational age <34 weeks.
* ≥2 symptoms suggestive of lactose intolerance: abdominal distension, abdominal pain, diarrhea, or diaper/nappy dermatitis.
* Feeding intolerance defined by GRV >3 mL/kg or the specified vomiting/stool/abdominal-distension.

Exclusion Criteria:

* Severe congenital malformations, including GI or cardiac defects.
* NEC according to Bell's staging criteria.
* Congenital diarrhea.
* Hemodynamic instability requiring inotropes.
* Amino-acid-based or lactose-free formula.
* Guardian declines consent.

• Ola Galal, Study director, NICU of Ain shams university hospitals