Introduction: Lactoferrin (LF) is a protective protein present in milk with anti-infective and immune-modulating properties. Objectives: The aim of this study was to determine the association of maternal LF intake and mother’s own milk intake in the first 10 days of life on the prevention of late-onset sepsis (LOS), necrotizing enterocolitis (NEC), or death in the first 8 weeks of life in newborns with a birth weight <2,000 g. Methods: A retrospective cohort study was conducted, with the exposure being the consumption of mother’s own LF and mother’s own milk in the first 10 days of life, and the outcome being LOS, NEC, or death during days 11 and 56 of life, analyzed by Cox regression. Results: Two hundred and ninety-nine infants were enrolled, including 240 with human LF intake information. The average daily human LF intake over days 4–10 of life was 283 mg/kg/day (IQR 114–606 mg/kg/day). The hazard ratio (HR) of mother’s own milk LF intake ≥100 mg/kg/day in days 4–10 for LOS, NEC, or death was 0.297 (95% CI 0.156–0.568, p < 0.001); the adjusted HR was 0.752 (95% CI 0.301–1.877, p = 0.541). The adjusted HR of mother’s own milk cumulative intake (days 4–10) of 54–344 mL/kg (25–75 quartiles) for LOS, NEC, or death was 0.414 (95% CI 0.196–0.873, p = 0.02). Infants who developed an event (LOS, NEC, or death) had significantly less median daily human LF intake than those that did not (89 vs. 334 mg/kg/day, respectively, p < 0.0001). Conclusion: Consumption of higher amounts of mother’s own milk in the first days of life is associated with less infection, NEC, and death. Early human milk intake should be strongly encouraged in all newborns.

1.
Meinzen-Derr
J
,
Poindexter
B
,
Wrage
L
,
Morrow
AL
,
Stoll
B
,
Donovan
EF
.
Role of human milk in extremely low birth weight infants’ risk of necrotizing enterocolitis or death
.
J Perinatol
.
2009
Jan
;
29
(
1
):
57
62
.
[PubMed]
0743-8346
2.
Lechner
BE
,
Vohr
BR
.
Neurodevelopmental outcomes of preterm infants fed human milk: a systematic review
.
Clin Perinatol
.
2017
Mar
;
44
(
1
):
69
83
.
[PubMed]
0095-5108
3.
Ballard
O
,
Morrow
AL
.
Human milk composition: nutrients and bioactive factors
.
Pediatr Clin North Am
.
2013
Feb
;
60
(
1
):
49
74
.
[PubMed]
0031-3955
4.
Vogel
HJ
.
Lactoferrin, a bird’s eye view
.
Biochem Cell Biol
.
2012
Jun
;
90
(
3
):
233
44
.
[PubMed]
0829-8211
5.
Embleton
ND
,
Berrington
JE
,
McGuire
W
,
Stewart
CJ
,
Cummings
SP
.
Lactoferrin: antimicrobial activity and therapeutic potential
.
Semin Fetal Neonatal Med
.
2013
Jun
;
18
(
3
):
143
9
.
[PubMed]
1744-165X
6.
Ochoa
TJ
,
Sizonenko
SV
.
Lactoferrin and prematurity: a promising milk protein?
Biochem Cell Biol
.
2017
Feb
;
95
(
1
):
22
30
.
[PubMed]
0829-8211
7.
Manzoni
P
,
Rinaldi
M
,
Cattani
S
,
Pugni
L
,
Romeo
MG
,
Messner
H
, et al.;
Italian Task Force for the Study and Prevention of Neonatal Fungal Infections, Italian Society of Neonatology
.
Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial
.
JAMA
.
2009
Oct
;
302
(
13
):
1421
8
.
[PubMed]
0098-7484
8.
Manzoni
P
,
Stolfi
I
,
Messner
H
,
Cattani
S
,
Laforgia
N
,
Romeo
MG
, et al.;
Italian Task Force for the Study and Prevention of Neonatal Fungal Infections–the Italian Society of Neonatology
.
Bovine lactoferrin prevents invasive fungal infections in very low birth weight infants: a randomized controlled trial
.
Pediatrics
.
2012
Jan
;
129
(
1
):
116
23
.
[PubMed]
0031-4005
9.
Manzoni
P
,
Meyer
M
,
Stolfi
I
,
Rinaldi
M
,
Cattani
S
,
Pugni
L
, et al.
Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial
.
Early Hum Dev
.
2014
Mar
;
90
Suppl 1
:
S60
5
.
[PubMed]
0378-3782
10.
Akin
IM
,
Atasay
B
,
Dogu
F
,
Okulu
E
,
Arsan
S
,
Karatas
HD
, et al.
Oral lactoferrin to prevent nosocomial sepsis and necrotizing enterocolitis of premature neonates and effect on T-regulatory cells
.
Am J Perinatol
.
2014
Dec
;
31
(
12
):
1111
20
.
[PubMed]
0735-1631
11.
Kaur
G
,
Gathwala
G
.
Efficacy of Bovine Lactoferrin Supplementation in Preventing Late-onset Sepsis in low Birth Weight Neonates: A Randomized Placebo-Controlled Clinical Trial
.
J Trop Pediatr
.
2015
Oct
;
61
(
5
):
370
6
.
[PubMed]
0142-6338
12.
Sherman
MP
,
Adamkin
DH
,
Niklas
V
,
Radmacher
P
,
Sherman
J
,
Wertheimer
F
, et al.
Randomized Controlled Trial of Talactoferrin Oral Solution in Preterm Infants
.
J Pediatr
.
2016
Aug
;
175
:
68
73.e3
.
[PubMed]
0022-3476
13.
Barrington
KJ
,
Assaad
MA
,
Janvier
A
.
The Lacuna Trial: a double-blind randomized controlled pilot trial of lactoferrin supplementation in the very preterm infant
.
J Perinatol
.
2016
Aug
;
36
(
8
):
666
9
.
[PubMed]
0743-8346
14.
Ochoa
TJ
,
Zegarra
J
,
Cam
L
,
Llanos
R
,
Pezo
A
,
Cruz
K
, et al.;
NEOLACTO Research Group
.
Randomized controlled trial of lactoferrin for prevention of sepsis in peruvian neonates less than 2500 g
.
Pediatr Infect Dis J
.
2015
Jun
;
34
(
6
):
571
6
.
[PubMed]
0891-3668
15.
Griffiths
J
,
Jenkins
P
,
Vargova
M
,
Bowler
U
,
Juszczak
E
,
King
A
, et al.;
ELFIN trial investigators group
.
Enteral lactoferrin supplementation for very preterm infants: a randomised placebo-controlled trial
.
Lancet
.
2019
Feb
;
393
(
10170
):
423
33
.
[PubMed]
0140-6736
16.
Pammi
M
,
Suresh
G
.
Enteral lactoferrin supplementation for prevention of sepsis and necrotizing enterocolitis in preterm infants
.
Cochrane Database Syst Rev
.
2017
Jun
;
6
(
6
):
CD007137
.
[PubMed]
1469-493X
17.
Ochoa
TJ
,
Zegarra
J
,
Belomo
S
,
Carcamo
C
,
Cam
L
,
Castañeda
A
, et al.;
NEOLACTO Research Group
.
Randomized trial of lactoferrin for sepsis prevention and neurodevelopment impairment in infants [{LT}]2000g
.
J Pediatr
. under review
2019
.0022-3476
18.
Turin
CG
,
Zea-Vera
A
,
Rueda
MS
,
Mercado
E
,
Carcamo
CP
,
Zegarra
J
, et al.;
NEOLACTO Research Group
.
Lactoferrin concentration in breast milk of mothers of low-birth-weight newborns
.
J Perinatol
.
2017
May
;
37
(
5
):
507
12
.
[PubMed]
0743-8346
19.
Corpeleijn
WE
,
Kouwenhoven
SM
,
Paap
MC
,
van Vliet
I
,
Scheerder
I
,
Muizer
Y
, et al.
Intake of own mother’s milk during the first days of life is associated with decreased morbidity and mortality in very low birth weight infants during the first 60 days of life
.
Neonatology
.
2012
;
102
(
4
):
276
81
.
[PubMed]
1661-7800
20.
Patel
AL
,
Johnson
TJ
,
Engstrom
JL
,
Fogg
LF
,
Jegier
BJ
,
Bigger
HR
, et al.
Impact of early human milk on sepsis and health-care costs in very low birth weight infants
.
J Perinatol
.
2013
Jul
;
33
(
7
):
514
9
.
[PubMed]
0743-8346
21.
Trend
S
,
Strunk
T
,
Hibbert
J
,
Kok
CH
,
Zhang
G
,
Doherty
DA
, et al.
Antimicrobial protein and Peptide concentrations and activity in human breast milk consumed by preterm infants at risk of late-onset neonatal sepsis
.
PLoS One
.
2015
Feb
;
10
(
2
):
e0117038
.
[PubMed]
1932-6203
22.
Zea-Vera
A
,
Turin
CG
,
Ochoa
TJ
.
[Unifying criteria for late neonatal sepsis: proposal for an algorithm of diagnostic surveillance]
.
Rev Peru Med Exp Salud Publica
.
2014
Apr
;
31
(
2
):
358
63
.
[PubMed]
1726-4642
23.
Rai
D
,
Adelman
AS
,
Zhuang
W
,
Rai
GP
,
Boettcher
J
,
Lönnerdal
B
.
Longitudinal changes in lactoferrin concentrations in human milk: a global systematic review
.
Crit Rev Food Sci Nutr
.
2014
;
54
(
12
):
1539
47
.
[PubMed]
1040-8398
24.
Furman
L
,
Taylor
G
,
Minich
N
,
Hack
M
.
The effect of maternal milk on neonatal morbidity of very low-birth-weight infants
.
Arch Pediatr Adolesc Med
.
2003
Jan
;
157
(
1
):
66
71
.
[PubMed]
1072-4710
25.
Sisk
PM
,
Lovelady
CA
,
Dillard
RG
,
Gruber
KJ
,
O’Shea
TM
.
Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants
.
J Perinatol
.
2007
Jul
;
27
(
7
):
428
33
.
[PubMed]
0743-8346
26.
Johnson
TJ
,
Patra
K
,
Greene
MM
,
Hamilton
M
,
Dabrowski
E
,
Meier
PP
, et al.
NICU human milk dose and health care use after NICU discharge in very low birth weight infants
.
J Perinatol
.
2019
Jan
;
39
(
1
):
120
8
.
[PubMed]
0743-8346
27.
Manzoni
P
,
Militello
MA
,
Rizzollo
S
,
Tavella
E
,
Messina
A
,
Pieretto
M
,
Boano
E
,
Carlino
M
,
Tognato
E
,
Spola
R
,
Perona
A
,
Maule
MM
,
García Sánchez
R
,
Meyer
M
,
Stolfi
I
,
Pugni
L
,
Messner
H
,
Cattani
S
,
Betta
PM
,
Memo
L
,
Decembrino
L
,
Bollani
L
,
Rinaldi
M
,
Fioretti
M
,
Quercia
M
,
Tzialla
C
,
Laforgia
N
,
Mosca
F
,
Magaldi
R
,
Mostert
M
,
Farina
D
,
Tarnow-Mordi
W
;
Italian Task Force for the Study Prevention of Neonatal Fungal Infections
; the Italian Society of Neonatology. Is Lactoferrin More Effective in Reducing Late-Onset Sepsis in Preterm Neonates Fed Formula Than in Those Receiving Mother's Own Milk? Secondary Analyses of Two Multicenter Randomized Controlled Trials. Am J Perinatol.
2019
;36(S 02):S120-S125.
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