Oral lactoferrin to prevent nosocomial sepsis and necrotizing enterocolitis of premature neonates and effect on T-regulatory cells.
OBJECTIVE
Lactoferrin (LF) is effective in the prevention of sepsis in very low birth weight (VLBW) neonates. T-regulatory cells (Tregs) are important subsets of T lymphocytes that control pathogen-specific immune responses and are essential for intestinal immune homoeostasis. The aim of the present study is to determine whether oral LF at a dosage of 200 mg/d reduces nosocomial sepsis episodes and necrotizing enterocolitis (NEC) in premature infants and to evaluate the possible effects of LF on Treg levels.


METHODS
In this prospective, placebo-controlled, double-blind, randomized trial, infants either VLBW or born before 32 weeks were assigned to receive either placebo (n = 25), or 200 mg LF (n = 25) daily throughout hospitalization. Episodes of culture proven nosocomial sepsis and NEC were recorded. The level of FOXP3 + CD4 + CD25hi lymphocytes was studied by flow cytometry at birth and discharge. A third comparison was made with healthy term neonates (n = 16).


RESULTS
Fewer sepsis episodes were observed in LF-treated infants (4.4 vs. 17.3/1,000 patient days, p = 0.007) with none developing NEC, without statistical significance. Treg levels at birth and discharge were similar, while preterm infants showed significantly lower levels than term controls. However, individual increases in Treg levels were higher in the LF group.


CONCLUSIONS
LF prophylaxis reduced nosocomial sepsis episodes. Treg levels in preterm infants were lower than in term infants and an increase of Treg levels under LF prophylaxis was observed. Increase in Treg levels can be the mechanism for protective effects of LF on nosocomial sepsis.
Division of Neonatology, School of Medicine, Ankara University, Ankara, Turkey.
Ilke Mungan
IM
Akin
Division of Neonatology, School of Medicine, Ankara University, Ankara, Turkey.
Begum
B
Atasay
Division of Pediatric Allergy and Immunology, School of Medicine, Ankara University, Ankara, Turkey.
Figen
F
Dogu
Division of Neonatology, School of Medicine, Ankara University, Ankara, Turkey.
Emel
E
Okulu
Division of Neonatology, School of Medicine, Ankara University, Ankara, Turkey.
Saadet
S
Arsan
Division of Pediatric Allergy and Immunology, School of Medicine, Ankara University, Ankara, Turkey.
H Deniz
HD
Karatas
Division of Pediatric Allergy and Immunology, School of Medicine, Ankara University, Ankara, Turkey.
Aydan
A
Ikinciogullari
Division of Neonatology, School of Medicine, Ankara University, Ankara, Turkey.
Tomris
T
Turmen
D000284:Administration, Oral; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003428:Cross Infection / Q000517:prevention & control*; D004311:Double-Blind Method; D020345:Enterocolitis, Necrotizing / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000517:prevention & control*; D019102:Infant, Very Low Birth Weight; D007781:Lactoferrin / Q000008:administration & dosage / Q000627:therapeutic use*; D018655:Lymphocyte Count; D008297:Male; D011446:Prospective Studies; D018805:Sepsis / Q000517:prevention & control*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
D000890:Anti-Infective Agents; D007781:Lactoferrin