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

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.

Predictive gene testing for Huntington disease and other neurodegenerative disorders.

BACKGROUND: Controversies exist around predictive testing (PT) programmes in neurodegenerative disorders. AIMS: This study sets out to answer the following questions relating to Huntington disease (HD) and other neurodegenerative disorders: differences between these patients in their PT journeys, why and when individuals withdraw from PT, and decision-making processes regarding reproductive genetic testing. METHODS: A case series analysis of patients having PT from the multidisciplinary Western Australian centre for PT over the past 20 years was performed using internationally recognised guidelines for predictive gene testing in neurodegenerative disorders. RESULTS: Of 740 at-risk patients, 518 applied for PT: 466 at risk of HD, 52 at risk of other neurodegenerative disorders - spinocerebellar ataxias, hereditary prion disease and familial Alzheimer disease. Thirteen percent withdrew from PT - 80.32% of withdrawals occurred during counselling stages. Major withdrawal reasons related to timing in the patients' lives or unknown as the patient did not disclose the reason. Thirty-eight HD individuals had reproductive genetic testing: 34 initiated prenatal testing (of which eight withdrew from the process) and four initiated pre-implantation genetic diagnosis. There was no recorded or other evidence of major psychological reactions or suicides during PT. CONCLUSIONS: People withdrew from PT in relation to life stages and reasons that are unknown. Our findings emphasise the importance of: (i) adherence to internationally recommended guidelines for PT; (ii) the role of the multidisciplinary team in risk minimisation; and (iii) patient selection.