Abstract
BackgroundSeveral 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).MethodsWe 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.ResultsNine 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.ConclusionsLimited 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.
Highlights
Complications of preterm birth were the leading cause of death in children under five worldwide, accounting for 35% of neonatal death (Liu et al, 2012; Chawanpaiboon et al, 2019)
Our meta-analyses indicated that enteral lactoferrin supplementation was not associated with a reduction in late-onset sepsis in all infants
Our meta-analysis found that enteral lactoferrin supplementation could reduce the incidence of late-onset sepsis in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants, it was not associated with a reduction in late-onset sepsis in all infants
Summary
Complications of preterm birth were the leading cause of death in children under five worldwide, accounting for 35% of neonatal death (Liu et al, 2012; Chawanpaiboon et al, 2019). The late-onset infection (occurring >72 hours after birth) is the most common serious complication associated with hospital care for preterm infants (Kaufman and Fairchild, 2004; ELFIN Trial Investigators Group, 2019), which can increase the risk of mortality and acute morbidities, including necrotizing enterocolitis, retinopathy of prematurity, and bronchopulmonary dysplasia, especially it is always associated with worse neurodevelopment (Stoll et al, 2004; Stoll et al, 2005; Bassler et al, 2009; Shane et al, 2017). We systematically evaluated the effect of enteral lactoferrin supplementation in preterm infants through a meta‐analysis with trial sequential analysis (TSA)
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