Stage II NEC,
all-cause mortality and LOS, and improve feed tolerance in preterm very
low birth weight (VLBW) infants [1]. No other intervention in neonatal
medicine comes close to probiotics in terms of the effect size for NEC
and mortality, and supporting evidence from research and clinical
practice [2].
Careful scrutiny of the literature reveals only few
issues that are sustaining the debate about probiotics for preterm
infants. These include the view that probiotic effects are
strain-specific (i.e. all meta-analyses in this field are null
and void!), the difficulty in accessing safe and clinical proven
probiotic products, and the risk of probiotic sepsis. Almost all other
issues, including ‘We don’t know how probiotics work’, ‘Probiotics are
not needed if the infant is fed breastmilk – the nature’s synbiotic, or
when the baseline incidence of NEC is low’, ‘The PIPs trial showed that
not all probiotic strains are effective, and challenged the previous
meta-analyses’, ‘There is not enough data on extremely low birth weight
(ELBW) infants, and probiotics may not have significant benefits in this
population’, have been addressed over the last few years [3-7].
Probiotic sepsis is easy to treat compared to sepsis by other
potentially disastrous (e.g. gram negative) organisms. If
contamination of the control arm underestimates the true effects of
probiotic in RCTs, the results of the cluster RCT by Totsu, et al.
[8] are reassuring. Substantial evidence indicates that probiotic
supplementation also benefits ELBW infants [9].
In this issue of Indian Pediatrics, Shashidhar,
et al. [10] report the effect of probiotic supplementation on the
time to full feeds (Primary outcome) in preterm VLBW (Birth
weight: 750-1499 g) infants randomly allocated to receive either breast
milk with a multi-strain probiotic (Lactobacillus acidophilus,
Lactobacillus rhamnosus, Bifidobacterium longum and Saccharomyces
boulardii once a day; dose: 1.25×10
1. Dermyshi E, Wang Y, Yan C, Hong W, Qiu G, Gong X,
et al. The "Golden Age" of probiotics: A systematic review and
meta-analysis of randomized and observational studies in preterm
infants. Neonatology. 2017;112:9-23.
2. Ofek Shlomai N, Deshpande G, Rao S, Patole S.
Probiotics for preterm neonates: what will it take to change clinical
practice? Neonatology. 2014;105:64-70.
3. Jacobs SE, Tobin JM, Opie GF, Donath S, Tabrizi
SN, Pirotta M, et al,; ProPrems Study Group. Probiotic effects on
late-onset sepsis in very preterm infants: a randomized controlled
trial. Pediatrics. 2013;132:1055-62.
4. Samuels N, van de Graaf R, Been JV, de Jonge RC,
Hanff LM, Wijnen RM, et al. Necrotising enterocolitis and
mortality in preterm infants after introduction of probiotics: A
quasi-experimental study. Sci Rep. 2016;6:31643.
5. Repa A, Thanhaeuser M, Endress D, Weber M, Kreissl
A, Binder C, et al. Probiotics (Lactobacillus acidophilus and
Bifidobacterium infantis) prevent NEC in VLBW infants fed breast milk
but not formula [Corrected]. Pediatr Res. 2015;77:381-8.
6. Karthikeyan G, Bhat BV. The PiPS (Probiotics in
Preterm Infants Study) trial – Controlling the confounding factor of
cross-contamination unveils significant benefits. Indian Pediatr.
2017;54:162.
7. Deshpande G, Rao S, Athalye-Jape G, Conway P,
Patole S. Probiotics in very preterm infants: the PiPS trial. Lancet.
2016;388:655.
8. Totsu S, Yamasaki C, Terahara M, Uchiyama A,
Kusuda S; Probiotics Study Group in Japan. Bifidobacterium and enteral
feeding in preterm infants: cluster-randomized trial. Pediatr Int.
2014;56:714-9.
9. Denkel LA, Schwab F, Garten L, Geffers C,
Gastmeier P, Piening B. Protective effect of dual-strain probiotics in
preterm infants: A multi-center time series analysis. PLoS One.
2016;11:e0158136.
10. Shashidhar A, Suman Rao PN, Nesargi S, Bhat S,
Chandrakala BS. Probiotics for promoting feed tolerance in very low
birth weight neonates – A randomized controlled trial. Indian Pediatr.
2017;54:363-7.
11. Althabe F, Belizán JM, McClure EM, Hemingway-Foday
J, Berrueta M, Mazzoni A, et al. A population-based, multifaceted
strategy to implement antenatal corticosteroid treatment versus standard
care for the reduction of neonatal mortality due to preterm birth in
low-income and middle-income countries: the ACT cluster-randomised
trial. Lancet. 2015;385:629-39.
12. California Dairy Research Foundation. Sanders ME.
Is it time to consider generic probiotic effects? Available from:
http://cdrf.org/2013/03/01/is-it-time-to-consider-generic-probiotic-effects/.
Accessed March 30, 2017.
13. GanguliK, Walker WA. Probiotics in the prevention
of necrotizing enterocolitis. J Clin Gastroenterol. 2011; 45: S133-S138.