Studying the effect of probiotics on intestinal colonization of pathogenic bacteria and Candida in very low birth weight premature infants admitted to the neonatal intensive care unit.

Determining the role of probiotics in bacterial and candida intestinal colonization in very low birth weight premature infants admitted to the neonatal intensive care unit

A controlled clinical trial with parallel groups, without blinding, randomized, on 130 patients. The rand function of Excel software was used for randomization.

A single-center, unblinded, randomized trial in the neonatal intensive care unit (NICU). VLBW infants receive either the probiotic *Lactobacillus reuteri* or no intervention for 5 days. Stool samples are examined for pathogen colonization on day 6. Families and physicians are unaware of the type of grouping. The study will be conducted at Shahid Motahari Hospital, Urmia.

Inclusion criteria: Premature infants with low birth weight (birth weight between 1000 and 1500 grams) Gestation age less than 32 weeks Admission to the neonatal intensive care unit (NICU) in the first 72 hours of life Exclusion criteria: Patient's parents' lack of consent Infant with digestive disorders after entering the study (intestinal obstruction, severe digestive diseases, etc.) Drug allergy Mortality

Infants were randomly assigned to two control groups, which included two subgroups of breastfed infants and formula-fed infants, and probiotic recipients, which included two subgroups of breastfed infants And infants who are fed formula will be allocated. From the time of starting feeding, five drops of probiotic Lactobacillus reuteri (Procid) will be given to infants daily for 5 days. On the sixth day, the infants' stool will be collected

The primary outcome in this study is a comparison of intestinal colonization in the probiotic group compared to the control group. Secondary outcomes include stool exam.

Randomization in this study will be carried out using a computer-generated random number sequence created in Microsoft Excel (version …), which will be executed by a research assistant not involved in participant recruitment or clinical care to ensure allocation concealment. Acknowledging the type of feeding as a significant and influential variable, the randomization process will be stratified based on two distinct strata: 'breastfed infants' and 'formula-fed infants'. Within each of these feeding strata, infants will be randomly allocated in a 1:1 ratio to either the intervention group, receiving the probiotic supplement, or the control group, receiving a placebo. This stratified randomization approach ensures a balanced distribution of infants with different feeding patterns across both study groups, thereby enabling a robust and valid comparison of the probiotic's effect.