Difficulties in developmental follow-up of preterm neonates in a randomised-controlled trial of Bifidobacterium breve M16-V - Experience from Western Australia

Abstract

Background: Probiotics may be neuroprotective for preterm neonates due to their anti-inflammatory effects and ability to facilitate nutrition.

Aim: To assess long-term effects of early probiotic supplementation on neuropsychological development in preterm infants.

Study design: Follow up study.

Subjects: Children at age 3 to 5 years who had participated as preterm infants (<33 week) in the randomised controlled trial.

Outcomes: Primary: Continuous early learning composite measure derived from the Mullen's Scale of Early Learning (MSEL). Other outcomes were assessed by the Developmental, Dimensional and Diagnostic Interview, Developmental NEuroPSYchological assessment-2nd Edition, Parental questionnaires using children's communication checklist-2nd edition, social responsiveness scale, and Vineland Adaptive Behavioural Scales-2nd edition.

Measures: Continuous scores derived from all the measures.

Results: 67 children of the 159 participants (42%) (Probiotic: 36/79, Placebo: 31/80) were followed-up for at least one neuropsychological assessment. All six assessments were completed in 18/31 (58.1%) of the control vs. 11/36 (30.6%) probiotic group children. Multivariable analysis of MSEL composite score showed no evidence of probiotic effect univariately, or after adjustment for gestation, intrauterine growth restriction, Apgar <7 at 5 min and age at assessment (adjusted mean effect in probiotic group: -2.7, 95% CI -8.5-3.0, p = 0.349).

Conclusion: There was no significant effect on neurodevelopment of children assessed at the age of 3 to 5 years who participated as preterm neonates in the RCT of B. breve M-16V. The validity of these results is limited by the reduced sample size due to high rate of loss to follow up.

Keywords: Children; Follow up; Neurodevelopment; Preterm neonates; Probiotic; Trial.