Probiotics, prematurity and neurodevelopment: follow-up of a randomised trial

Susan E Jacobs, Leah Hickey, Susan Donath, Gillian F Opie, Peter J Anderson, Suzanne M Garland, Jeanie L Y Cheong, ProPremsStudy Groups, S E Jacobs, L Hickey, G F Opie, S M Garland, Jly Cheong, S Donath, P J Anderson, L Gold, K L Sia, J M Tobin, S N Tabrizi, M Pirotta, Mlk Tang, C J Morley, K Tan, A Lewis, A Veldman, E Carse, J Travadi, Imr Wright, D A Osborn, J Sinn, J Bowen, J Levison, J A Stack, A G Depaoli, N C Austin, B A Darlow, J M Alsweiler, M J Buksh, Susan E Jacobs, Leah Hickey, Susan Donath, Gillian F Opie, Peter J Anderson, Suzanne M Garland, Jeanie L Y Cheong, ProPremsStudy Groups, S E Jacobs, L Hickey, G F Opie, S M Garland, Jly Cheong, S Donath, P J Anderson, L Gold, K L Sia, J M Tobin, S N Tabrizi, M Pirotta, Mlk Tang, C J Morley, K Tan, A Lewis, A Veldman, E Carse, J Travadi, Imr Wright, D A Osborn, J Sinn, J Bowen, J Levison, J A Stack, A G Depaoli, N C Austin, B A Darlow, J M Alsweiler, M J Buksh

Abstract

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.

Keywords: Neurodevelopment.

Conflict of interest statement

Competing interests: None decalred.

Figures

Figure 1
Figure 1
Trial follow-up profile.

References

    1. AlFaleh K, Anabrees J. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2014;4.
    1. Jacobs SE, Tobin JM, Opie GF, et al. . Probiotic effects on late-onset sepsis in very preterm infants: a randomized controlled trial. Pediatrics 2013;132:1055–62.
    1. Rao SC, Athalye-Jape GK, Deshpande GC, et al. . Probiotic Supplementation and Late-Onset Sepsis in Preterm Infants: A Meta-analysis. Pediatrics 2016;137:e20153684–1-16.
    1. Doyle LW, Roberts G, Anderson PJ, et al. . Outcomes at age 2 years of infants < 28 weeks' gestational age born in Victoria in 2005. J Pediatr 2010;156:49–53.
    1. Hintz SR, Kendrick DE, Stoll BJ, et al. . Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics 2005;115:696–703.
    1. Hooper LV, Midtvedt T, Gordon JI. How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annu Rev Nutr 2002;22:283–307.
    1. Ley RE, Bäckhed F, Turnbaugh P, et al. . Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A 2005;102:11070–5.
    1. Turnbaugh PJ, Ley RE, Mahowald MA, et al. . An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006;444:1027–131.
    1. Cryan JF, O’Mahony SM. The microbiome-gut-brain axis: from bowel to behavior. Neurogastroenterol Motil 2011;23:187–92.
    1. Kelly JR, Kennedy PJ, Cryan JF, et al. . Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci 2015;9:392
    1. Gareau MG, Sherman PM, Walker WA. Probiotics and the gut microbiota in intestinal health and disease. Nat Rev Gastroenterol Hepatol 2010;7:503–14.
    1. Chakraborti CK. New-found link between microbiota and obesity. World J Gastrointest Pathophysiol 2015;6:110–9.
    1. Manichanh C, Rigottier-Gois L, Bonnaud E, et al. . Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 2006;55:205–11.
    1. Jiang H, Ling Z, Zhang Y, et al. . Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun 2015;48:186–94.
    1. Hill C, Guarner F, Reid G, et al. . Expert consensus document. The International scientific association for probiotics and prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 2014;11:506–14.
    1. Bercik P, Verdu EF, Foster JA, et al. . Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology 2010;139:2102–12.
    1. Desbonnet L, Garrett L, Clarke G, et al. . Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience 2010;170:1179–88.
    1. Chou IC, Kuo HT, Chang JS, et al. . Lack of effects of oral probiotics on growth and neurodevelopmental outcomes in preterm very low birth weight infants. J Pediatr 2010;156:393–6.
    1. Romeo MG, Romeo DM, Trovato L, et al. . Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome. J Perinatol 2011;31:63–9.
    1. Sari FN, Eras Z, Dizdar EA, et al. . Do oral probiotics affect growth and neurodevelopmental outcomes in very low-birth-weight preterm infants? Am J Perinatol 2012;29:579–86.
    1. Garland SM, Tobin JM, Pirotta M, et al. . The ProPrems trial: investigating the effects of probiotics on late onset sepsis in very preterm infants. BMC Infect Dis 2011;11:210
    1. Palisano R, Rosenbaum P, Walter S, et al. . Development and reliability of a system to classify gross motor function in children with cerebral palsy. Dev Med Child Neurol 1997;39:214–23.
    1. Bayley N. Bayley Scales of Infant and Toddler Development, The Psycholgical Corporation. 3rd ed Harcourt Assessment, Inc, 2006.
    1. Anderson PJ, De Luca CR, Hutchinson E, et al. . Underestimation of developmental delay by the new Bayley-III Scale. Arch Pediatr Adolesc Med 2010;164:352–6.
    1. Anderson PJ, Burnett A. Assessing developmental delay in early childhood - concerns with the Bayley-III scales. Clin Neuropsychol 2017;31:371–81.
    1. Wechsler D. Wechsler Primary and Preschool Scale of Intelligence. 3rd ed Psychological Corporation, 2002.
    1. Henderson SE, Sugden DA. Movement Assessment Battery for Children. 2nd ed: (Movement ABC-2): Pearson Assessment, 2007.
    1. Carter AS, Briggs-Gowan MJ, Jones SM, et al. . The Infant-Toddler Social and Emotional Assessment (ITSEA): factor structure, reliability, and validity. J Abnorm Child Psychol 2003;31:495–514.
    1. Treyvaud K, Anderson VA, Howard K, et al. . Parenting behavior is associated with the early neurobehavioral development of very preterm children. Pediatrics 2009;123:555–61.
    1. Rothman KJ. Epidemiology M. Boston: Little, Brown, 1986.
    1. Lumley T, Kronmal R, Ma S. Relative risk regression in medical research: models, contrasts, estimators, and algorithms. UW Biostatistics Working Paper Series. 2006.
    1. Oike H, Aoki-Yoshida A, Kimoto-Nira H, et al. . Dietary intake of heat-killed Lactococcus lactis H61 delays age-related hearing loss in C57BL/6J mice. Sci Rep 2016;6:23556
    1. Cristobal R, Oghalai JS. Hearing loss in children with very low birth weight: current review of epidemiology and pathophysiology. Arch Dis Child Fetal Neonatal Ed 2008;93:F462–F468.
    1. Messaoudi M, Lalonde R, Violle N, et al. . Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. Br J Nutr 2011;105:755–64.
    1. Steenbergen L, Sellaro R, van Hemert S, et al. . A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain Behav Immun 2015;48:258–64.
    1. Davari S, Talaei SA, Alaei H, et al. . Probiotics treatment improves diabetes-induced impairment of synaptic activity and cognitive function: behavioral and electrophysiological proofs for microbiome-gut-brain axis. Neuroscience 2013;240:287–96.
    1. Shanahan F. Molecular mechanisms of probiotic action: it’s all in the strains!. Gut 2011;60:1026–7.
    1. Roberts G, Howard K, Spittle AJ, et al. . Rates of early intervention services in very preterm children with developmental disabilities at age 2 years. J Paediatr Child Health 2008;44:276–80.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe