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Enteral Lactoferrin Supplementation for Preventing Sepsis and Necrotizing Enterocolitis in Preterm Infants: A
Ya Gao1,2, Liangying Hou3, Cuncun Lu1,2
1Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
Insights
Enteral lactoferrin supplementation did not significantly prevent sepsis or necrotizing enterocolitis (NEC) in preterm infants. However, it may reduce sepsis in low birth weight infants, but more research is needed.
Area of Science:
- Neonatal Medicine
- Pediatric Gastroenterology
- Immunology
Background:
- Enteral lactoferrin supplementation is explored for preventing sepsis and necrotizing enterocolitis (NEC) in preterm infants.
- Existing clinical trial evidence on its efficacy and safety remains inconclusive.
- A systematic meta-analysis with trial sequential analysis (TSA) was conducted to clarify these effects.
Purpose of the Study:
- To systematically evaluate the efficacy and safety of enteral lactoferrin supplementation in preterm infants.
- To determine the impact on key neonatal morbidities including sepsis and NEC.
- To assess the overall evidence quality using TSA.
Main Methods:
- A comprehensive search of six databases identified relevant randomized controlled trials (RCTs).
- Meta-analysis using a random-effects model was performed with RevMan 5.3 software.
- Trial sequential analysis (TSA), subgroup, and meta-regression analyses were employed.
Main Results:
- Nine RCTs involving 3515 infants were analyzed.
- No significant reduction in late-onset sepsis, NEC stage II/III, or all-cause mortality was observed.
- A significant reduction in sepsis incidence was noted in infants with birth weight <1500g (RR = 0.43).
- Evidence for other outcomes like BPD, ROP, and infections was insufficient.
Conclusions:
- Enteral lactoferrin shows potential for reducing sepsis in very low birth weight preterm infants.
- It did not demonstrate efficacy in preventing NEC stage II/III, mortality, or other adverse events.
- Current evidence is insufficient to guide clinical practice, necessitating further research.
Background:
Several clinical trials investigated the effects of enteral lactoferrin supplementation on the prevention of sepsis and necrotizing enterocolitis (NEC) in preterm infants, but the efficacy and safety remain disputed. Therefore, we systematically evaluated the effect of enteral lactoferrin supplementation in preterm infants through a meta‑analysis with trial sequential analysis (TSA).
Methods:
We searched six databases to identify randomized controlled trials (RCTs) that evaluated the effects of lactoferrin supplementation compared with placebo or no intervention in preterm infants. RevMan version 5.3 software was used to estimate pooled relative risks (RRs) with the random-effects model. TSA, subgroup analyses, and meta-regression analyses were also performed.
Results:
Nine RCTs with 3515 samples were included. With low to moderate quality of evidence, compared with placebo, enteral lactoferrin supplementation did not significantly decrease the incidences of late-onset sepsis (RR = 0.63, 95% CI: 0.38 to 1.02, P = 0.06), NEC stage II or III (RR = 0.68, 95% CI: 0.30 to 1.52, P = 0.35), all-cause mortality (RR = 0.89, 95% CI: 0.51 to 1.57, P = 0.69), bronchopulmonary dysplasia (RR = 1.01, 95% CI: 0.90 to 1.13, P = 0.92), retinopathy of prematurity (RR = 0.80, 95% CI: 0.49 to 1.32, P = 0.38), invasive fungal infection (RR = 0.27, 95% CI: 0.02 to 3.94, P = 0.34), intraventricular hemorrhage (RR = 1.40, 95% CI: 0.39 to 5.08, P = 0.61), and urinary tract infection (RR = 0.35, 95% CI: 0.11 to 1.06, P = 0.06). Subgroup analysis revealed that lactoferrin significantly reduced the incidence of sepsis in infants with a birth weight below 1500 g (RR = 0.43, 95% CI: 0.22 to 0.84, P = 0.01). TSAs of the primary outcomes showed that the evidence is insufficient and further data is required.
Conclusions:
Limited evidence suggested that enteral lactoferrin supplementation was associated with a reduction of late-onset sepsis in infants with a birth weight below 1500g, however, did not decrease the incidence of NEC stage II or III, all-cause mortality, and other adverse events in preterm infants. The present evidence was insufficient to inform clinical practice.
