School-Age Neurodevelopmental and Atopy Outcomes in Extremely Preterm Infants: Follow-Up from the Single Versus Triple-Strain Bifidobacterium Randomized Controlled Trial.

Follow-up rates at five years were high and comparable between the single-strain and triple-strain probiotic groups.

• Single-strain (SS: B. breve M-16V) follow-up rate was 89.2%
• Triple-strain (TS: B. breve M-16V, B. longum subsp. infantis-M63, B. longum subsp. longum-BB536) follow-up rate was 95%
• This was a follow-up of the SiMPro randomized controlled trial enrolling extremely preterm infants (<28 weeks gestation)

Rates of severe neurodevelopmental impairment based on Full Scale Intelligence Quotient were comparable between the single-strain and triple-strain groups.

• Severe impairment (FSIQ < 70) occurred in 7.4% of the SS group versus 4.3% of the TS group
• The difference was not statistically significant (p = 0.68)
• Cognition was assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) at approximately five years of age
• Logistic regression was used and adjusted for Socio-Economic Indexes for Areas (SEIFA) centiles

Disability rates were comparable between the single-strain and triple-strain probiotic groups.

• No disability was reported in 66.7% of the SS group versus 55.4% of the TS group
• Disability rates were modeled using logistic regression adjusted for SEIFA centiles
• The difference between groups was not statistically significant

Behavioral and executive function outcomes were comparable between the two probiotic groups.

• Behavior was assessed using the Strengths and Difficulties Questionnaire
• Executive function was assessed using the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P)
• Total difficulty scores and BRIEF-P executive indices were comparable between the SS and TS groups
• A linear mixed model was used for longitudinal outcomes

Growth, BMI, and blood pressure outcomes at school age were comparable between the single-strain and triple-strain probiotic groups.

• Anthropometric measures were assessed as part of the five-year follow-up outcomes
• Blood pressure was also measured at the five-year follow-up
• No statistically significant differences were found between the SS and TS groups for any growth or BP parameter
• A linear mixed model was used for these longitudinal outcomes

Atopy-related outcomes at six to seven years of age were comparable between the single-strain and triple-strain probiotic groups.

• Atopy-related outcomes were evaluated using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire
• Assessment was conducted at six to seven years of age
• No statistically significant differences were found between the SS and TS groups for atopy-related outcomes

Both single-strain and triple-strain Bifidobacterium probiotic formulations were considered safe based on comparable long-term outcomes.

• The study assessed extremely preterm infants (<28 weeks gestation) originally enrolled in the SiMPro randomized controlled trial
• Outcomes assessed included neurodevelopment, growth, blood pressure, and atopy at school age
• Neither formulation showed superiority over the other across any of the measured long-term outcomes