Role of probiotics VSL#3 in prevention of suspected sepsis in low birthweight infants in India: a randomised controlled trial

Abstract

ObjectivesTo assess the effect of the probiotic VSL#3 in prevention of neonatal sepsis in low birthweight (LBW) infants.DesignRandomised, double-blind, placebo-controlled trial.SettingCommunity setting in rural India.ParticipantsLBW infants aged 3–7 days.InterventionsInfants were randomised to receive probiotic (VSL#3, 10 billion colony-forming units (cfu)) or placebo for 30 days, and were followed up for 2 months.Main outcome measurePossible serious bacterial infection (PSBI) as per the Integrated Management of Neonatal Childhood Illnesses algorithm, as diagnosed by fieldworkers/physicians.Results668 infants were randomised to VSL#3 and 672 to placebo. By intention-to-treat analysis, the risk of PSBI among infants in the overall population of LBW infants was not statistically significant (RR 0.79 (95% CI 0.56 to 1.03)). Probiotics reduced median days of hospitalisation (6 days vs 3 days in probiotics) (p=0.018) but not the risk of hospitalisation (RR 0.66 (95% CI 0.42 to 1.04). The onset of PSBI in 10% of infants occurred on the 40th day in the probiotics arm versus the 25th day in the control arm (p=0.063).ConclusionsDaily supplementation of LBW infants with probiotics VSL#3 (10 billion cfu) for 30 days led to a non-significant 21% reduction in risk of neonatal sepsis. A larger study with sufficient power and a more specific primary end point is warranted to confirm the preventive effect of VSL#3 on neonatal sepsis in LBW infants.Trial registration numberThe study is registered at the Clinical Trial Registry of India (CTRI/2008/091/000049).

Lactiplantibacillus plantarum–Nomad and Ideal Probiotic

“…The observed 42% reduction in sepsis was significantly greater than the anticipated reduction and facilitated early termination of the trial. The results of this trial stand in contrast to two other studies that used probiotics to target sepsis in very preterm infants (Jacobs et al, 2013;Costeloe et al, 2016) and a third, smaller trial, conducted in low birth weight infants in India (Sinha et al, 2015). These differences may be related to probiotic choice, administration schedule or the addition of a prebiotic supplement, but suggest that administration of L. plantarum may be capable of reducing the risk of sepsis/pSBI and lower respiratory infections for neonates in developing countries.…”

Lactiplantibacillus plantarum–Nomad and Ideal Probiotic

“…The observed 42% reduction in sepsis was significantly greater than the anticipated reduction and facilitated early termination of the trial. The results of this trial stand in contrast to two other studies that used probiotics to target sepsis in very preterm infants (Jacobs et al, 2013;Costeloe et al, 2016) and a third, smaller trial, conducted in low birth weight infants in India (Sinha et al, 2015). These differences may be related to probiotic choice, administration schedule or the addition of a prebiotic supplement, but suggest that administration of L. plantarum may be capable of reducing the risk of sepsis/pSBI and lower respiratory infections for neonates in developing countries.…”

Evaluating the Efficacy of a Multistrain Probiotic Supplementation for Prevention of Neonatal Sepsis in 0-2 Months Old Low Birth Weight Infants in India – The ‘ProSPoNS’ Study Protocol for a Phase III, Multicentric, Randomized, Double-Blind, Placebo-Controlled Trial.

“…No changes have been done in the probiotic composition, its dose, and the duration of administration [22]. Changes in the gut colonization pattern between the participants in probiotic and placebo arm were observed in the previous study; however, the changes were not significant [22]. Therefore, this study proposes to conduct the gut colonization studies in a larger sample size to substantiate the clinical results.…”

“…This study proposes to use a new, standardized, and a more convenient dosage form that is foolproof as far as contamination is concerned and may allow future up-scaling if the intervention proved to be is efficacious based on the results of this trial. No changes have been done in the probiotic composition, its dose, and the duration of administration [22]. Changes in the gut colonization pattern between the participants in probiotic and placebo arm were observed in the previous study; however, the changes were not significant [22].…”

Effects of Probiotics in Preterm Infants: A Network Meta-analysis

“…In total, 12,320 participants were included in these trials and randomly allocated into intervention groups (n = 6577) and placebo group (n = 5743). Samples were drawn from 19 different locations including America, 26-32 Asia, [33][34][35][36][37][38][39][40][41][42][43][44][45][46] Europe, 8,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] Africa, 67 and Australia. 68,69 Most RCTs included comparison of two arms (n = 41), but some included three (n = 3) or four (n = 1) arms.…”

Lactiplantibacillus plantarum–Nomad and Ideal Probiotic

“…The observed 42% reduction in sepsis was significantly greater than the anticipated reduction and facilitated early termination of the trial. The results of this trial stand in contrast to two other studies that used probiotics to target sepsis in very preterm infants (Jacobs et al, 2013;Costeloe et al, 2016) and a third, smaller trial, conducted in low birth weight infants in India (Sinha et al, 2015). These differences may be related to probiotic choice, administration schedule or the addition of a prebiotic supplement, but suggest that administration of L. plantarum may be capable of reducing the risk of sepsis/pSBI and lower respiratory infections for neonates in developing countries.…”

Evaluating the Efficacy of a Multistrain Probiotic Supplementation for Prevention of Neonatal Sepsis in 0-2 Months Old Low Birth Weight Infants in India – The ‘ProSPoNS’ Study Protocol for a Phase III, Multicentric, Randomized, Double-Blind, Placebo-Controlled Trial.

“…No changes have been done in the probiotic composition, its dose, and the duration of administration [22]. Changes in the gut colonization pattern between the participants in probiotic and placebo arm were observed in the previous study; however, the changes were not significant [22]. Therefore, this study proposes to conduct the gut colonization studies in a larger sample size to substantiate the clinical results.…”

“…This study proposes to use a new, standardized, and a more convenient dosage form that is foolproof as far as contamination is concerned and may allow future up-scaling if the intervention proved to be is efficacious based on the results of this trial. No changes have been done in the probiotic composition, its dose, and the duration of administration [22]. Changes in the gut colonization pattern between the participants in probiotic and placebo arm were observed in the previous study; however, the changes were not significant [22].…”

Effects of Probiotics in Preterm Infants: A Network Meta-analysis

“…In total, 12,320 participants were included in these trials and randomly allocated into intervention groups (n = 6577) and placebo group (n = 5743). Samples were drawn from 19 different locations including America, 26-32 Asia, [33][34][35][36][37][38][39][40][41][42][43][44][45][46] Europe, 8,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] Africa, 67 and Australia. 68,69 Most RCTs included comparison of two arms (n = 41), but some included three (n = 3) or four (n = 1) arms.…”

Lactiplantibacillus plantarum–Nomad and Ideal Probiotic

“…The observed 42% reduction in sepsis was significantly greater than the anticipated reduction and facilitated early termination of the trial. The results of this trial stand in contrast to two other studies that used probiotics to target sepsis in very preterm infants (Jacobs et al, 2013;Costeloe et al, 2016) and a third, smaller trial, conducted in low birth weight infants in India (Sinha et al, 2015). These differences may be related to probiotic choice, administration schedule or the addition of a prebiotic supplement, but suggest that administration of L. plantarum may be capable of reducing the risk of sepsis/pSBI and lower respiratory infections for neonates in developing countries.…”

Evaluating the Efficacy of a Multistrain Probiotic Supplementation for Prevention of Neonatal Sepsis in 0-2 Months Old Low Birth Weight Infants in India – The ‘ProSPoNS’ Study Protocol for a Phase III, Multicentric, Randomized, Double-Blind, Placebo-Controlled Trial.

“…No changes have been done in the probiotic composition, its dose, and the duration of administration [22]. Changes in the gut colonization pattern between the participants in probiotic and placebo arm were observed in the previous study; however, the changes were not significant [22]. Therefore, this study proposes to conduct the gut colonization studies in a larger sample size to substantiate the clinical results.…”

“…This study proposes to use a new, standardized, and a more convenient dosage form that is foolproof as far as contamination is concerned and may allow future up-scaling if the intervention proved to be is efficacious based on the results of this trial. No changes have been done in the probiotic composition, its dose, and the duration of administration [22]. Changes in the gut colonization pattern between the participants in probiotic and placebo arm were observed in the previous study; however, the changes were not significant [22].…”

Effects of Probiotics in Preterm Infants: A Network Meta-analysis

“…In total, 12,320 participants were included in these trials and randomly allocated into intervention groups (n = 6577) and placebo group (n = 5743). Samples were drawn from 19 different locations including America, 26-32 Asia, [33][34][35][36][37][38][39][40][41][42][43][44][45][46] Europe, 8,[47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] Africa, 67 and Australia. 68,69 Most RCTs included comparison of two arms (n = 41), but some included three (n = 3) or four (n = 1) arms.…”