Objective To determine the impact of one probiotics combination on the neurodevelopment of very preterm children at 2–5 years corrected gestational age (CA).
Design Follow-up study of survivors of a double-blinded, placebo-controlled, randomised trial of probiotic effects on late-onset sepsis in very preterm infants that found reduced necrotising enterocolitis.
Setting 10 tertiary perinatal centres in Australia and New Zealand.
Patients 1099 very preterm infants born <32 weeks’ gestation and weighing <1500 g.
Intervention Probiotics (Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis) or placebo administered from birth until discharge home or term CA, whichever came sooner.
Main outcome measures Major neurodevelopmental impairment comprised any of moderate/severe cerebral palsy (Gross Motor Function Classification System score 2–5), motor impairment (Bayley-III Motor Composite Scale <–2SD or Movement Assessment Battery for Children <15th centile if >42 months’ CA), cognitive impairment (Bayley-III Composite Cognitive or Language Scales <–2SD or Wechsler Preschool and Primary Scale of Intelligence Full Scale Intelligence Quotient <–2SD if >42 months’ CA), blindness or deafness.
Results Outcome data were available for 735 (67%) participants, with 71 deaths and 664/1028 survivors assessed at a mean age of 30 months. Survival free of major neurodevelopmental impairment was comparable between groups (probiotics 281 (75.3%) vs placebo 271 (74.9%); relative risk 1.01 (95% CI 0.93 to 1.09)). Rates of deafness were lower in probiotic-treated children (0.6% vs 3.4%).
Conclusion Administration of the probiotics combination Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis to very preterm babies from soon after birth until discharge home or term CA did not adversely affect neurodevelopment or behaviour in early childhood.
Trial registration number Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN012607000144415.
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Contributors SJ, LH and JC were involved in study design, literature review and planning data analysis. SJ prepared the first version of the manuscript assisted by LH. SD performed all data analyses. SJ, LH and GO conducted and coordinated the study. GO and PA assisted with planning assessments and with interpretation of results. SMG designed the original ProPrems randomised controlled trial. All authors reviewed and approved the final draft.
Funding This work was supported by the National Health and Medical Research Council of Australia grant numbers 454629 and 1028050; SJ is also supported by Early Career Fellowship number 1073103, PA by Senior Research Fellowship number 1081288 and JC by Early Career Fellowship number 1053787).
Disclaimer The probiotic combination ’ABC Dophilus Powder for Infants' was supplied at cost by Solgar, USA, which had no role in the trial design, conduct, data management or analysis or writing the manuscript. The authors have no financial disclosures relevant to this article to disclose.
Competing interests None decalred.
Patient consent Written informed consent was obtained from parents or guardians both for the original study and the neurodevelopmental follow-up. However, they were not BMJ patient consent forms.
Ethics approval Human research ethics committees at participating 10 centres.
Provenance and peer review Not commissioned; externally peer reviewed.
Collaborators Group Information: Members of The ProPrems Study Groups are as follows. ProPrems Neuro Steering Group: SE Jacobs (principal investigator), L Hickey (chief investigator), GF Opie (chief investigator), SM Garland (chief investigator), JLY Cheong (chief investigator), S Donath (associate investigator), PJ Anderson (associate investigator), L Gold (associate investigator), KL Sia (associate investigator). ProPrems Steering Group: SM Garland (principal investigator), SE Jacobs (chief investigator), JM Tobin (chief investigator), SN Tabrizi (chief investigator), M Pirotta (chief investigator), S Donath (associate investigator), GF Opie (associate investigator), MLK Tang (associate investigator), CJ Morley (associate investigator). Trial Statistician: S Donath, Clinical Epidemiology and Biostatistics Unit, Murdoch Childrens Research Institute, Melbourne, Australia. Participating Hospitals and Investigators: SM Garland, SE Jacobs, CJ Morley, SN Tabrizi, L Hickey, JLY Cheong, The Royal Women’s Hospital; GF Opie, Mercy Hospital for Women; K Tan, A Lewis, A Veldman, E Carse, Monash Health; L Hickey, PJ Anderson, MLK Tang, Royal Children’s Hospital: all in Melbourne, Australia; J Travadi, IMR Wright, John Hunter Children’s Hospital; DA Osborn, Royal Prince Alfred Hospital; J Sinn, J Bowen, Royal North Shore Hospital; J Levison, JA Stack, Liverpool Hospital; – all in New South Wales, Australia; AG DePaoli, Royal Hobart Hospital, Tasmania, Australia; NC Austin, BA Darlow, Christchurch Women’s Hospital, University of Otago, Christchurch, New Zealand; JM Alsweiler, MJ Buksh, Auckland City Hospital and The Liggins Institute, University of Auckland, Auckland, New Zealand.
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