Necrotizing

Enterocolitis:
Can Probiotics
Help?
Eric Wyatt, BSN, RNC-NIC

MSNC 511
Evidence-Based Practice: Role of Theory and Research
University of San Diego

December 5, 2022
Necrotizing Enterocolitis (NEC)
A gastrointestinal disease
with serious intestinal
inflammation and injury
thought to be secondary to
bowel ischemia,
immaturity, and infection
(Kim 2020)
Probiotics:
A group of living organisms that can
reduce pathogenic bacteria while
promoting beneficial intestinal flora
(NIH, 2019)

Stage 1 (Suspected) Stage 2 (Definite) Stage 3 (Advanced)

A B A B A B
• Apnea • Brady- • Absent • Thrombo- • Hypo- • Pneumo-
• Lethargy cardia Bowel cytopenia tension peritoneum
• Distention • Bloody Sounds • Ascites • Neutro-
• Emesis Stool • Tender- • Intestinal penia
• Ileus ness Dilation • Acidosis

(Kim, 2020)
 PICOT Question
In preterm neonates (<37 weeks gestation), how does
probiotic administration (of any strain) compared to no
probiotic administration affect the incidence of necrotizing
enterocolitis during the course of the hospital stay?

Outcome Measurements

NEC Length of Stay

Sepsis Time to Full Feeds Mortality

 Search Strategy
Databases
• Health Source: Nursing / Academic Edition
• CINAHL (Cumulative Index to Nursing and Allied
Health Literature)
• PubMed

Keywords Exclusion Criteria

• Neonate • Human Studies

• NEC / Necrotizing Enterocolitis • English Language
• Probiotic • Published within the
• NICU last 5 years
• Preterm • Inpatient Setting
 Evidence
Level Type Quality

#1 Meta-Analysis (2019) A

I #5 Meta-Analysis (2017) A

#3 Randomized Control Trial (2019) C

#2 Meta-Analysis and Systematic

II B
Review (2021)

#4 Nonexperimental Retrospective
III B
Study (2021)
 1 Bi, Yan, Yang, Li and Cui (2019) China

• Meta-Analysis Key Points

• I.A • Probiotic administration lowers the risk

of developing NEC
• “Probiotic strategies to
• Study does not explore appropriate
prevent necrotizing
dosage
enterocolitis in preterm
infants: a meta • Does not explore methods of
analysis” administration

• Included 34 studies • A mixture of Lactobacilli and

representing 9161 Bifidobacteria showed the most benefit
preterm neonates
• Routine probiotic supplementation
(RPS) also lowered rates of sepsis and
mortality
 2 Deshmukh and Patole (2021) Australia

Key Points
• Systematic Review and
Meta-Analysis • Moderate- to low-quality evidence
indicates that RPS reduces the
incidence of NEC, mortality, length of
• II.B
stay and time to full feeds

• “Prophylactic probiotic • Probiotic mixtures were more effective

supplementation for than single-strain strategies
preterm neonates – a (Saccharomyces)
systematic review and
meta-analysis of • All studies included were observational,
cohort, and/or case-control
nonrandomized studies”
• No significant difference in mortality
• Included 30 studies and/or length of stay in ELBW neonates
representing 77,018
preterm neonates • The studies had wide variance in
strain, dose and duration
 Akhter, Noor, Hussain, Ahmed, Irshad
3 and Chisti (2019) Pakistan

• Randomized Control Key Points

Trial
• No benefit with RPS was observed
• I.C
• Strain utilized was Lactobacillus
• “Role of enteral
probiotics for • Standard dosage of 3 x10^9 units daily
prevention of neonatal
• Neonates were only observed for 7 days
necrotizing
enterocolitis in preterm • Did not discuss demographics of both
infants: a randomized groups to support intervention as the
placebo controlled trial determinative factor

• 220 preterm neonates • Was unable to eliminate RPS as

providing a detrimental effect with
over a 6-month period
some neonates developing NEC
 Zhu, Yuan, Gao, X. Wang, J. Wang, L.
4 Wang and Deng (2021) China

• Nonexperimental Key Points

Retrospective Study
• RPS lowers the risk of developing NEC
• III.B and the effective duration of use is 10.5
days or greater

• “The role of probiotics • By comparing neonates that developed

prophylaxis duration in NEC with those that didn’t, RPS
preventing necrotizing duration was inversely related
enterocolitis: a single-
center retrospective • The study was conducted at one center
study”
• The NEC group was small which lowered
the statistical power of conclusions
• 237 preterm neonates
over a 5-year period • There was a significant difference
related to gestation among
the two groups
 Sun, Marwah, Westgarth, Buys,
5 Ellwood and Gray (2017) Australia

• Meta-Analysis Key Points

• I.A • RPS reduces the risk of developing NEC,

sepsis, length of stay, and mortality
• “Effects of probiotics on
necrotizing enterocolitis, • RPS should have a dosage of 10x10^9
units daily of multiple strains
sepsis, intraventricular
hemorrhage, mortality, • Little exploration of specific strains
length of hospital stay, (Enterococcus, Streptococcus
and weight gain in very thermophilus)
preterm infants: a meta-
analysis” • Only included very preterm infants

• RPS was most effective when taken

• 32 studies representing
with breast milk and formula
8,492 preterm neonates
Findings
In preterm neonates (<37 weeks
gestation), how does probiotic The evidence shows
administration (of any strain) that RPS can and
compared to no probiotic does reduce the risk
administration affect the incidence of developing NEC in
of necrotizing enterocolitis during preterm neonates.
the course of the hospital stay?

Inconsistencies
What is the appropriate When should therapy
dosage? begin and end?

How best should it be

What strain should be used?
administered?
 Implications
There is good evidence that However, it is
utilizing probiotics in the preterm currently difficult to
neonate population provides a assess what best
benefit and/or a protective factor evidence-based
against the risk of NEC. protocol should be
followed.
Potential Research Project
• Preterm neonate (subgroup of VLBW)
• Lactobacilli and Bifidobacteria mixture 10x10^9 vs placebo.
• Administered with breast milk and formula when feeding is initiated
• Should have a duration of at least 10.5 days
• The outcome measurement of NEC as defined by Bell’s staging
• A risk assessment and ethical analysis should be performed
 References
Akhter, M. K., Noor, M., Hussain, G., Ahmed, T., Irshad, S., & Chishti, A. L. (2019). Role of enteral probioitcs for
prevention of necrotizing enterocolitis (NEC) in preterm infants: a randomized placebo controlled trial. Annals
of King Edward Medical University, 25(3), 1–5.

Bi, L.-wee, Yan, B.-lei, Yang, Q.-yu, Li, M.-miao, & Cui, H.-lei. (2019). Probiotic strategies to prevent necrotizing
enterocolitis in preterm infants: A meta-analysis. Pediatric Surgery International, 35(10), 1143–1162.
https://doi.org/10.1007/s00383-019-04547-5

Deshmukh, M., & Patole, S. (2021). Prophylactic probiotic supplementation for preterm neonates—a systematic
review and meta-analysis of nonrandomized studies. Advances in Nutrition, 12(4), 1411–1423.
https://doi.org/10.1093/advances/nmaa164

Kim, J. (2020, June 18). Neonatal necrotizing enterocolitis: Clinical features and diagnosis - UpToDate.
UpToDate. https://www.uptodate.com/contents/5019#!

NIH, (2019, July 5). Probiotics: What You Need To Know | NCCIH. National Center for Complementary and
Integrative Health. https://www.nccih.nih.gov/health/probiotics-what-you-need-to-know

Sun, J., Marwah, G., Westgarth, M., Buys, N., Ellwood, D., & Gray, P. H. (2017). Effects of probiotics on
necrotizing enterocolitis, sepsis, intraventricular hemorrhage, mortality, length of hospital stay, and
weight gain in very preterm infants: A meta-analysis. Advances in Nutrition: An International Review
Journal, 8(5), 749–763. https://doi.org/10.3945/an.116.014605

Zhu, K., Yuan, L., Gao, H., Wang, X., Wang, J., Wang, L., & Deng, F. (2021). The role of probiotics prophylaxis
duration in preventing necrotizing enterocolitis: A single-center retrospective study. Iranian Journal of
Pediatrics, 31(5). https://doi.org/10.5812/ijp.114996