Probiotics

1. Abdul Razak bin Husain
Paediatrics, Hospital Keningau
January 20th, 2021

3.  Necrotising enterocolitis and sepsis are two major contributors for preterm,
neonatal mortality
 NEC alone is a devastating acquired disease affecting gastrointestinal of most, but
not exclusively to premature infant
 Characterised by iscahemic necrosis of intestinal mucosa
 Excessive inflammatory process, and
 Invasion of enteric gas-forming microorganism
 Aetiology is still not fully explained, multifactorial
 Including, immaturity of host defense
 Abnormal bacterial colonisation

4.  Infant lives in a sterile intrauterine environment
 The quick colonization happened right after delivery by variety of ingested
environmentals and maternal flora
 Gestational age
 Route of delivery
 Maternal bacterial flora
 Antenatal and postanatal antibiotics
 Hygiene of neonatal environment
 Type of feeding
 Lack of microbial diversity in the bowel of premature infant will lead to abnormal
pattern of bacterial colonization
 This in comparison to a healthy breastmilk fed term infant

6.  PROBIOTICS
 Defined by World Helath Organisations: live microorganisms which, when administered
in adequate amount, confer a health benefits on the host
 An ideal probiotics must be healthy, resist degradation of by gastric acids and bile
salt, adhere to intestinal cells wall, non invasive and non pathogenic, non
invasive, modulate immune response, sensitive to antibiotics without development
of resistance,
 Commonly used as protbiotics:
 Lactobacillus sp. ; Bifidobacterium sp. ; Streptococcus thermophiles
 Yeast, eg: Saccharomyces boulardii

7.  RANGE OF PROBIOTIC EFFECTS
 Reduce intestinal permeability
 Increase mucosal bacteria to bacteria and bacterial products
 Prevention of translocation of bacteria and bacteria products
 Upregulation of local and systemic immunity
 Normalisation of microflora
 Competitive exclusive of potential pathogens
 Protection of mucosa from colonization by pathogens
 Lactic acid, propionic acid and acetic acid suppressing growth of pathogen
 Increased anti-flammatory cytokines
 Augmentation of IgA mucosal responses

12.  Metanalysis of RCT and observational studies
 12 studies included involving 10,800 premature neonates
 LBW (<2500g)
 Preterm of less than 37 week
 Administration of probiotics of at least 7 days
 Infant with birth defects, or major congenital anomalies (eg heart disease,
myelomenigocoele)
 Primary outcome interest is NEC stage II and III
 Others, includes : all cause mortality, sepsis, and long term neurological
development

13.  Smaller proportion of preterm neo- nates developed NEC (169/5,144, 3.3%) compared to the
control group (325/5,656, 5.7%).
The use of prophylactic probiotics was associated with a significant decreased risk of NEC (risk
ratio, RR = 0.55, 95% CI, 0.39–0.78; p = 0.0006) compared to the control group
 Mortality rate was 7.6% (354/4,629) compared to the control group with 10% (353/3,510).
This demonstrated a significant reduction in the risk of mortality
(RR = 0.72, 95% CI, 0.61–0.85; p < 0.0001)
 Data for sepsis:
No statistically significant reduced risk in the group given prophylactic probiotics
(RR = 0.86, 95% CI, 0.74–1.00; p = 0.05) compared to the control group.

15.  RCT and observational total of 44 studies
 30 RCT using 8622 infants; 14 Observational studies using 13, 779 infants
 VLBW (<1500g)
 Preterm of less than 34week
 Administration of probiotics within 10 days
 Clinical outcome examined includes NEC stage II and above, all cause mortality
and late onset of sepsis (proven with blood culture)

16.  NEC STAGE II – III
 RCT: Twenty-nine trials reported data on NEC (stage II–III) in VLBW infants. The
administration of probiotics significantly reduced the incidence of severe NEC
(RR 0.57, 95% CI 0.47–0.70, p < 00001)
 OS: Fourteen studies reported on severe stage II–III NEC. The administration of probiotics
significantly reduced the incidence of severe stage II–III NEC in VLBW infants
(RR 0.51, 95% CI 0.37–0.70, p < 0001)

17.  LATE ONSET OF SEPSIS
 RCT: Twenty-eight trials reported on late-onset sepsis. The administration of probiotics
reduced the rate of sepsis in the pooled effect by 12%
(typical RR 0.88, 95% CI 0.80–0.97, p = 0.01)
 OS: Eight studies reported on late-onset sepsis. The administration of probiotics reduced
the incidence of sepsis in VLBW infants by 19%
(RR 0.81, 95% CI 0.69–0.96, p = 0.01 )
 MORTALITY
 RCT: Twenty-seven trials reported on mortality. The administration of probiotics
significantly reduced the rate of mortality in the VLBW infants
(typical RR 0.77, 95% CI 0.65–0.92, p = 0.003)
 OS: Eleven studies reported on mortality. The administration of probiotics significantly
reduced the incidence of mortality in VLBW infants
(RR 0.71, 95% CI 0.62–0.81, p < 0001)

20.  Lactobacillus acidophilus BCMC® 12130,
 Lactobacillus casei BCMC® 12313,
 Lactobacillus lactis BCMC® 12451,
 Bifidobacterium bifidum BCMC® 02290,
 Bifidobacterium infantis BCMC® 02129,
 Bifidobacterium longum BCMC® 02120
 Started to be used in Likas from July 2020, for infant < 1.5kg

22.  Jae H Kim, Stephen AA; Neonatal Nectrotizing Enterocollitis: Prevention: Probiotics. UpToDate, July 2020, Topic
5040
 Rie Olsen, Gom Greisen; Prophylactic Probiotics for Preterm Infants: A Systematic Review and Meta-Analysis of
Observational Studies. Neonatology 2016;109:105–112
 Elda Dermyshie, Yizhong Wang; The “Golden Age” of Probiotics: A Systematic Review and Meta-Analysis of
Randomized and Observational Studies in Preterm Infants. Neonatology 2017;112:9–23
 Vrinda Nair, Amuchou SS; Review Article: Probiotics and Prebiotics: Role in Prevention of Nosocomial Sepsis in
Preterm Infants. International Journal of Pediatrics Volume 2013, Article ID 874726, 8p
 M Millar, M Wilks; Review: Probiotics for preterm infants? Arch Dis Child Fetal Neonatal Ed 2003;88:F354–F358
 Elaheh Amini, Hosein Dalili; The Effect of Probiotics in Prevention of Necrotising Enterocolitis in Preterm Neonates
in Comparison with Control Group. Iran J Pediatr. 2017 December; 27(6):e7663.

23. SELAMAT MENCUBA