School-Age Neurodevelopmental and Atopy Outcomes in Extremely Preterm Infants: Follow-Up from the Single Versus...

Background: Probiotic supplementation for very preterm infants is a common practice in many neonatal units. Assessing the effects of early postnatal exposure to probiotics on long-term neurodevelopment, growth, and atopy-related outcomes is important. Extremely preterm (EP: <28 weeks) infants enrolled in our previously reported randomized trial (SiMPro) comparing short-term effects of single (SS: B. breve M-16V) versus triple-strain (TS: B. breve M-16V, B. longum subsp. infantis-M63, B. longum subsp. longum-BB536) probiotic provided a unique opportunity to study this issue. Methods: This follow-up study assessed the five-year outcomes of SiMPro trial infants, including neurodevelopment (cognition (Full Scale Intelligence Quotient/ FSIQ using WPPSI-IV), behavior (Strengths and Difficulties Questionnaire), executive function (BRIEF-P)), growth (anthropometry) and blood pressure (BP). Atopy-related outcomes were evaluated at six to seven years using the ISAAC questionnaire. A linear mixed model was used for longitudinal outcomes. Impairment indicators were modeled using logistic regression and adjusted for Socio-Economic Indexes for Areas (SEIFA) centiles. Results: Follow-up rates (SS: 89.2% versus TS: 95%), neurodevelopmental outcomes [severe impairment (FSIQ < 70): SS: 7.4% versus TS: 4.3%; p = 0.68], growth, BMI, and BP were comparable between the SS and TS groups. The total difficulty score or BRIEF-P executive indices, disability rates (none: 66.7% versus 55.4%), and atopy-related outcomes were comparable between groups. Conclusions: Both TS and SS Bifidobacterium probiotic formulations were safe, with comparable neurodevelopmental, growth, and atopy-related outcomes at school age.