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

Abstract

BackgroundProbiotics may be neuroprotective for preterm neonates due to their anti-inflammatory effects and ability to facilitate nutrition. AimTo assess long-term effects of early probiotic supplementation on neuropsychological development in preterm infants. Study designFollow up study. SubjectsChildren at age 3 to 5 years who had participated as preterm infants (<33 week) in the randomised controlled trial. OutcomesPrimary: 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. MeasuresContinuous scores derived from all the measures. Results67 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). ConclusionThere 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.