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Meta-Analysis
. 2018 Aug;97(35):e11976.
doi: 10.1097/MD.0000000000011976.

Prophylactic lactoferrin for preventing late-onset sepsis and necrotizing enterocolitis in preterm infants: A PRISMA-compliant systematic review and meta-analysis

Yi He  1 , Luying Cao, Jialin Yu
Affiliations
Meta-Analysis

Prophylactic lactoferrin for preventing late-onset sepsis and necrotizing enterocolitis in preterm infants: A PRISMA-compliant systematic review and meta-analysis

Yi He et al. Medicine (Baltimore). 2018 Aug.

Abstract

Background: Currently, prophylactic use of drugs to promote a healthy gut microbiota and immune system in preterm infants is hot debated, among which lactoferrin is a promising supplementation. However, the effect and safety of lactoferrin to prevent late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants remains controversial.

Methods: Databases including Medline, Ovid-Embase, The Cochrane Library, CBM, CNKI, and VIP database of Chinese Journal were searched to collect randomized controlled trials (RCTs) about lactoferrin for preventing LOS and NEC in preterm infants. Languages of included RCTs were restricted to English and Chinese. Meta-analysis was conducted by Rev Man 5.3 software. The Mantel-Haenszel method with random-effects model was used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs).

Results: A total of 9 RCTs, involving 1834 patients, were included. Pooled analysis showed that prophylactic lactoferrin could significantly reduce the incidence all culture-proven LOS (41/629 [6.5%] vs 96/659 [15.3%]; RR 0.47; 95% CI 0.33-0.67; P < .01) and NEC (stage II or more) (9/448 [2.0%] vs 26/462 [5.6%]; RR 0.40; 95% CI 0.18-0.86; P < .01). Lactoferrin was also associated with a significantly decreased hospital-acquired infection (16/139 [11.5%] vs 35/140 [25%]; RR 0.47; 95% CI 0.27-0.80; P < .01); and infection-related mortality (4/474 [0.8%] vs 25/505 [4.9%]; RR 0.24; 95% CI 0.04-1.32; P < .01, I = 53%). Lactoferrin could shorten time to reach full enteral feeding (weighted mean difference [WMD] = -2.11, 95% CI -3.12 to -1.10; P < .01) and showed a decreasing trend of duration of hospitalization (WMD = -1.69, 95% CI -6.87 to 3.50; P < .01; I = 95%). Lactoferrin did not have a significant effect on all-cause mortality (22/625 [3.5%] vs 35/647 [5.4%]; RR 0.70; 95% CI 0.38-1.30; P = .16; I = 13%). None of the included trials reported any confirmed adverse effects caused by the supplemented lactoferrin or probiotics.

Conclusion: Current evidence indicates that lactoferrin could significantly reduce the incidence of NEC and LOS, and decrease the risk of hospital-acquired infection and infection-related mortality in premature infants without obvious adverse effects.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Selection process for the studies included in the meta-analysis.
Figure 2
Figure 2
Risk of bias graph.
Figure 3
Figure 3
Risk of bias summary.
Figure 4
Figure 4
Outcome 1.1: Effect of lactoferrin on necrotizing enterocolitis in preterm neonates.
Figure 5
Figure 5
Outcome 1.2: Effect of lactoferrin on late-onset sepsis in preterm neonates.
Figure 6
Figure 6
Outcome 1.3: Effect of lactoferrin on hospital-acquired infection in preterm neonates.
Figure 7
Figure 7
Outcome 1.4: Effect of lactoferrin on infection-related mortality in preterm neonates.
Figure 8
Figure 8
Outcome 1.5: Effect of lactoferrin on days to achieve full enteral feeding in preterm neonates.
Figure 9
Figure 9
Quality of evidence using GRADE method.
See this image and copyright information in PMC

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