Endpoint

Necrotising enterocolitis incidence

CAT:outcome/necrotising-enterocolitis-incidencereported in risk ratio8 findings from 6 compounds

What moved it

8 findings · 6 compounds · 4 null · by evidence strength

Compound	Direction	Findings	Strongest evidence
L-arginine	down	3	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
all-cis-docosa-4,7,10,13,16,19-hexaenoic acid	down	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
L-cysteine	no effect	1	Evidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.
caffeine	no effect	1	Evidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.
L-glutamine	no effect	1	Evidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.
Zn(2+)	no effect	1	Evidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.

Reported to move it

4 findings

all-cis-docosa-4,7,10,13,16,19-hexaenoic acid — decreases
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.Finding
“Confirmed NEC was lower in infants from the DHA-group compared with the control-group (0/100 vs. 7/100, p = 0.007) with a RR of 0.93 (95% CI 0.881 to 0.981, p = 0.008); there was a risk difference of −7% (95% CI −12.00 to −1.99), and a number needed to treat of 15 (95% CI 8.3 to 50).”
Quoted verbatim from Efficacy of Docosahexaenoic Acid for the Prevention of Necrotizing Enterocolitis in Preterm Infants: A Randomized Clinical Trial..
Study

RCT
Duration

14 days
Dose

75 mg DHA/kg body weight daily for 14 days from the first enteral feed
Population

Preterm infants (birthweight 1000-1500 g) dosed enterally by orogastric tube; outcome measured in the same infants; per-protocol analysis; confirmed NEC defined as Bell stage IIa or greater (modified Walsh)
Effect 0.93 risk ratio, 95% CI 0.881 to 0.981
Efficacy of Docosahexaenoic Acid for the Prevention of Necrotizing Enterocolitis in Preterm Infants: A Randomized Clinical Trial.2021PMID:33671220An author is affiliated with a producerPermalink
L-arginine — decreases
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.Findingreplicated ×2
“L-arginine had a 59% reduction in the incidence of stage II and III NEC (RR 0.41, 95% CI 0.20 to 0.85, NNT = 9) compared with placebo (P = 0.02).”
Quoted verbatim from Arginine supplementation in prevention of necrotizing enterocolitis in the premature infant: an updated systematic review..
Study

meta-analysis
Population

preterm infants born at 34 weeks gestation or less with birth weight 1500 g or less; event definition is stage II and III NEC
Arginine supplementation in prevention of necrotizing enterocolitis in the premature infant: an updated systematic review.2014PMID:25205007Permalink
L-arginine — decreases
Very limitedEvidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.Findingreplicated ×2
“There was a statistically significant reduction in the risk of developing NEC (any stage) in the arginine group compared with the placebo group [RR 0.24 (95% CI 0.10, 0.61), RD -0.21 (95% CI -0.32, -0.09)].”
Quoted verbatim from Arginine supplementation for prevention of necrotising enterocolitis in preterm infants..
Study

meta-analysis
Population

preterm neonates given enteral or parenteral arginine supplementation vs placebo or no treatment, pooled from the single eligible trial identified by this review
Effect 0.24 risk ratio, 95% CI 0.1 to 0.61
Arginine supplementation for prevention of necrotising enterocolitis in preterm infants.2007PMID:17636753Permalink
L-arginine — decreases
Very limitedEvidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.Findingreplicated ×2
“There was a statistically significant reduction in the risk of developing NEC (any stage) in the arginine group compared with the placebo group (RR 0.24 [95% CI 0.10, 0.61], RD -0.21 [95% CI -0.32, -0.09]).”
Quoted verbatim from Arginine supplementation for prevention of necrotising enterocolitis in preterm infants..
Study

meta-analysis
Population

preterm neonates given enteral or parenteral arginine supplementation vs placebo or no treatment, pooled from the single eligible trial identified by this review
Effect 0.24 risk ratio, 95% CI 0.1 to 0.61
Arginine supplementation for prevention of necrotising enterocolitis in preterm infants.2004PMID:15495101Permalink

Measured, no effect detected

4 findings

L-cysteine — no detected effect on
ModerateEvidence strength: moderate. Human evidence with one recorded weakness, or capped at moderate by its design or by unread numbers.FindingNull result
“No difference was found in the CYS and ISO groups with regards to the percent of subjects diagnosed with necrotizing enterocolitis (29% vs. 24%, p=1), intraventricular hemorrhage grade III and IV (19% vs. 24%, p=1), and need for laser treatment for retinopathy of prematurity (24% vs. 24%, p=1).”
Quoted verbatim from Effect of High-Dose Cysteine Supplementation on Erythrocyte Glutathione: A Double-Blinded, Randomized Placebo-Controlled Pilot Study in Critically Ill Neonates..
Study

RCT
Dose

cysteine-HCl 121 mg/kg/day in parenteral nutrition with sodium acetate 2 mEq/kg/day
Population

Critically ill neonates on mechanical ventilation and parenteral nutrition (SNAP > 10); comparator is isonitrogenous additional parenteral amino acids without cysteine
Effect of High-Dose Cysteine Supplementation on Erythrocyte Glutathione: A Double-Blinded, Randomized Placebo-Controlled Pilot Study in Critically Ill Neonates.2016PMID:25139979Permalink
L-glutamine — no detected effect on
Very limitedEvidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.FindingNull result
“We found that glutamine supplementation does not have a statistically significant effect on the incidence of systemic infection (typical relative risk 1.02 (95% confidence interval 0.92 to 1.13); typical risk difference 0.01 (95% confidence interval -0.03 to 0.05)), necrotising enterocolitis (typical relative risk 1.02 (95% confidence interval 0.79 to 1.33); typical risk difference 0.00 (95% confidence interval -0.02 to 0.03)), days to full enteral nutrition (weighted mean difference -1.1 days (95% confidence interval -3.4 to 1.2)), or duration of hospital stay (weighted mean difference 0.65 days (95% confidence interval -2.9 to 4.2)).”
Quoted verbatim from Glutamine supplementation to prevent morbidity and mortality in preterm infants..
Study

meta-analysis
Population

very low birth weight preterm infants (pooled meta-analysis of six randomised trials, enteral and parenteral)
Effect 1.02 risk ratio, 95% CI 0.79 to 1.33
Glutamine supplementation to prevent morbidity and mortality in preterm infants.2005PMID:15674878Permalink
caffeine — no detected effect on
Very limitedEvidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.FindingNull result
“Seven trials assessing necrotising enterocolitis and four trials assessing feeding intolerance in our meta-analysis found no differences between caffeine and placebo (OR=1.007 (95% credible interval 0.021, 5.462), I2=97.4%, and OR=1.266 (95% credible interval 0.064, 28.326), I2=84.8%, respectively).”
Quoted verbatim from Gastrointestinal effects of caffeine in preterm infants: a systematic review and Bayesian meta-analysis..
Study

meta-analysis
Population

preterm infants; necrotising enterocolitis endpoint, 7 of 9 trials (Bayesian meta-analysis)
Effect 1.007 odds ratio, 95% CI 0.021 to 5.462
Gastrointestinal effects of caffeine in preterm infants: a systematic review and Bayesian meta-analysis.2024PMID:38649257Permalink
Zn(2+) — no detected effect on
Very limitedEvidence strength: very limited. Human evidence with major recorded weaknesses, or non-human, uncontrolled or unverified evidence.FindingNull result
“Enteral zinc supplementation may have little or no effect on common morbidities such as bronchopulmonary dysplasia (RR 0.66, 95% CI 0.31 to 1.40, 1 study, 193 infants; low-certainty evidence), retinopathy of prematurity (RR 0.14, 95% CI 0.01 to 2.70, 1 study, 193 infants; low-certainty evidence), bacterial sepsis (RR 1.11, 95% CI 0.60 to 2.04, 2 studies, 293 infants; moderate-certainty evidence), or necrotising enterocolitis (RR 0.08, 95% CI 0.00 to 1.33, 1 study, 193 infants; low-certainty evidence).”
Quoted verbatim from Enteral zinc supplementation for prevention of morbidity and mortality in preterm neonates..
Study

meta-analysis
Participants

193
Population

Hospitalised preterm infants given enteral zinc versus placebo or no supplementation; single study
Effect 0.08 risk ratio, 95% CI 0 to 1.33
Enteral zinc supplementation for prevention of morbidity and mortality in preterm neonates.2021PMID:33710626Permalink

How it is measured

Proportion of infants developing necrotising enterocolitis, staged by the modified Bell criteria. The stage counted as an event is recorded with each finding, most often Bell stage II or above.