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.

Breastmilk provides protection against infections and necrotizing enterocolitis (NEC) and improves neurodevelopment due to its multiple bioactive components [1-3]. Among these is lactoferrin (LF), a glycoprotein with anti-infective and immune-modulating effects [4-6]. There is currently high interest in studying the effects of bovine LF supplementation on the prevention of neonatal sepsis and NEC [7-16].

Our research group has recently conducted a randomized trial to evaluate the effect of daily supplementation of bovine LF on the prevention of neonatal late-onset sepsis (LOS) in <2,000 g newborns. The study failed to demonstrate a significant effect on the reduction of sepsis [17]. As part of the trial, we obtained breastmilk samples to measure human LF concentrations [18].

Previous studies have demonstrated that the consumption of colostrum and maternal breastmilk offers protection against sepsis in very low birth weight (VLBW) infants [19-21]. However, there is a gap in the knowledge of the true effects of the consumption of human LF on the protection against infections and death in premature newborns. The aims of this study were to determine the effect of mother’s own milk (MOM) LF (human LF) intake (aim 1) and MOM intake (aim 2) in the first 10 days of life on the prevention of neonatal LOS, NEC, or death in the first 8 weeks of life in newborns born <2,000 g and in the subgroup of VLBW infants.

This is a secondary analysis of the data from the NEOLACTO trial (NCT 01525316) [17]. Briefly, this was a randomized, double-blind, placebo-controlled study to evaluate the effect of oral supplementation of bovine LF in 414 newborns enrolled in the first 3 days of life in Lima. We requested a breastmilk sample in the first 6 days of life (colostrum) and between 7 and 14 days (transitional milk) to measure the concentration of human LF using a commercial ELISA kit (Assaypro, St. Charles, MO, USA) [18]. The study definitions were: culture-proven LOS, clinical signs and symptoms of infection, and a positive blood culture obtained after 72 h of life; probable sepsis or culture-negative infection, clinical signs and symptoms of infection plus at least 2 abnormal laboratory results; each LOS episode was classified based on a study algorithm [22]. For NEC we included NEC with Bell’s stage ≥2 [1].

To measure the effect of maternal LF intake on the prevention of sepsis we performed a retrospective cohort study. The exposure was the cumulative consumption of maternal LF (mg/kg) during days 4–10 of life measured by the daily consumption of MOM (mL/kg) multiplied by the concentration of LF in the colostrum and early transitional milk of each mother, which was taken as a homogenous value for the first 10 days of life. No donor milk was used in these hospitals. The volume of maternal milk was measured directly; mothers manually extracted the milk and the corresponding volume was given to the neonate in a syringe directly to the mouth or via a nasogastric tube. The outcome was the first episode of LOS (culture confirmed or probable sepsis), NEC, or death between day 11 and 56 of life.

Statistical Analysis

We performed a multivariate Cox regression model to estimate the effect of consumption of human LF (cumulative consumption in mg/kg) in the first 10 days of life on the risk of development of LOS, NEC, or death. The analysis was adjusted by: (1) breast milk consumption (cumulative intake in mL/kg during the days of exposure), (2) the percentage of breast milk consumption in relation to the total milk intake (breast milk + infant formula), and (3) human LF intake (cumulative breast milk intake in mL/kg during the days of exposure multiplied by the concentration of LF in colostrum [days 1–6] and early transitional milk [days 7–10]). The time to event was calculated from day 11 of life until discharge, day 56 of life (in the absence of an event), or the occurrence of the event. As we excluded all events prior to the completion of the exposure period, we excluded all infants with an event or discharge prior to day 11. Potentially confounding variables, supplementation of bovine LF (yes/no), gestational age (weeks), birth weight (grams), gender, hospital (1, 2, or 3), and age of milk sample collection were evaluated and added to the model one by one. In order to visualize the effect, we created a Kaplan-Meier survival curve. We analyzed the average daily human LF intake in 2 groups based on the quartiles. For aim 2, the analysis was adjusted by the percentage of human milk consumption and adjusted for the same confounding variables. For the Kaplan-Meier survival curve, we analyzed human milk intake in 3 groups, based on the quartiles.

Of the 414 newborns enrolled in the trial, we excluded 115 infants because they were discharged or had an event before day 11. The total number of eligible infants for the analysis was 299. The mean birth weight of enrolled infants was 1,410 ± 308 g, with a gestational age of 31 ± 2.7 weeks; 61.2% were VLBW, 81.3% were born by C-section, and 50.5% were randomized to bovine LF supplementation. Among the VLBW infants the mean birth weight was 1,214 ± 216 g and the mean gestational age was 29.8 ± 2.6 weeks. Information on human LF was available in 324 infants (277 colostrum samples and 47 early transitional milk); after exclusions, 240 infants were included in the analysis of human LF intake. There were 41 events during the outcome evaluation period (days 11–56 of life), including a total of 15 culture-confirmed sepsis episodes (5 CoNS, 3 E. coli, 2 Klebsiella, 2 Enterococcus, 2 Candida, 1 S. aureus).

The mean human LF concentration in colostrum and transitional milk was 14.4 ± 8.1 mg/mL. The concentrations of human LF varied over time (Fig. 1). For infants <2,000 g, the average daily human LF intake over days 4–10 of life was 283 mg/kg/day (interquartile range [IQR] 114–606). The intake of >100 mg/kg/day of human LF (approx. equivalent to the first quartile) over the exposure period was associated with fewer episodes of LOS, NEC, or death, as observed in the Kaplan-Meier survival curves (Fig. 2a), with a protective crude hazard ratio (HR; Table 1). For VLBW infants, the median daily human LF intake over days 4–10 of life was 178 mg/kg/day (IQR 74–391). The adjusted HRs were not significant (Table 1). For extremely low birth weight infants (<1,000 g) the median daily human LF intake over days 4–10 of life was 66 mg/kg/day (IQR 20–120). The adjusted HRs were not significant. We performed a secondary analysis including only the LF values from days 4–10 (12.7 ± 7.0 mg/mL), and applied this mean value to all infants (n = 299). With this analysis the adjusted HR of human LF intake ≥100 mg/kg/day for LOS, NEC, or death was 0.412 (95% CI 0.191–0.888, p = 0.024).

Table 1.

Effect of human LF intake on the prevention of LOS, NEC, or death

Effect of human LF intake on the prevention of LOS, NEC, or death
Effect of human LF intake on the prevention of LOS, NEC, or death
Fig. 1.

Concentration of human LF in the first 10 days of life in 240 mothers of infants <2,000 g.

Fig. 1.

Concentration of human LF in the first 10 days of life in 240 mothers of infants <2,000 g.

Close modal
Fig. 2.

Survival curves for LOS, NEC, and death by the amount of mother’s milk LF intake over days 4–10 of life (a; the line represents the average daily LF intake), and the amount of MOM intake over days 4–10 of life (b; the line represents the accumulative milk intake separated by quartiles).

Fig. 2.

Survival curves for LOS, NEC, and death by the amount of mother’s milk LF intake over days 4–10 of life (a; the line represents the average daily LF intake), and the amount of MOM intake over days 4–10 of life (b; the line represents the accumulative milk intake separated by quartiles).

Close modal

For infants <2,000 g the median cumulative intake of MOM (aim 2) over days 4–10 of life was 154 mL/kg (IQR 54–344). The percentage of human milk consumption was 77 ± 32%. The intake of more MOM over the exposure period was associated with fewer episodes of LOS, NEC, or death as observed in the Kaplan-Meier survival curves by quartiles (Fig. 2b). The adjusted HR of MOM cumulative intake (days 4–10) of 54–344 mL/kg (25–75 quartiles) for LOS, NEC, and death was 0.414 (95% CI 0.196–0.873, p = 0.02; Table 2). If we include only culture-confirmed sepsis in the outcome, the HR was not significant. For VLBW infants the median cumulative intake of MOM over days 4–10 of life was 92 mL/kg (IQR 38–202). The percentage of human milk consumption was 84 ± 28%, and the adjusted HR of MOM cumulative intake was also protective (p = 0.034; Table 2).

Table 2.

Effect of own MOM intake on the prevention of LOS, NEC, or death

Effect of own MOM intake on the prevention of LOS, NEC, or death
Effect of own MOM intake on the prevention of LOS, NEC, or death

When comparing the clinical and nutritional characteristics of the infants who developed an event (LOS, NEC, or death) or not, the infants who developed an event had significantly lower gestational age and birth weight and less intake of MOM (42 vs. 176 mL/kg) during the exposure period (Table 3). The infants that developed an event had less average daily human LF intake during the exposure period compared to the infants without an event (89 vs. 334 mg/kg/day in infants <2,000 g, p < 0.0001, and 77 vs. 184 mg/kg/day in VLBW infants, p = 0.003; Table 3; Fig. 3).

Table 3.

Clinical and nutritional characteristics in the first 10 days of life in infants with and without LOS, NEC, or death

Clinical and nutritional characteristics in the first 10 days of life in infants with and without LOS, NEC, or death
Clinical and nutritional characteristics in the first 10 days of life in infants with and without LOS, NEC, or death
Fig. 3.

Average daily human LF intake in mg/kg/day over days 4–10 among infants that developed an event (LOS, NEC, or death) or not, after day 10 of life. a Infants <2,000 g, n = 240 (37 cases or events and 203 controls with no event). b Infants <1,500 g, n = 141 (31 cases or events and 110 controls with no event).

Fig. 3.

Average daily human LF intake in mg/kg/day over days 4–10 among infants that developed an event (LOS, NEC, or death) or not, after day 10 of life. a Infants <2,000 g, n = 240 (37 cases or events and 203 controls with no event). b Infants <1,500 g, n = 141 (31 cases or events and 110 controls with no event).

Close modal

This study demonstrates that the consumption of human milk in the first days of life protects against infections and death in the first 8 weeks of life in infants <2,000 g and in VLBW infants. Neonates with higher human LF intake were less likely to have an event than neonates with lower intake. The daily human LF intake depends on the concentration of LF in milk and the amount of human milk intake. In our study the concentration of LF in milk was around 14 mg/mL (first 10 days of life) and around 13 mg/mL (days 4–10 of life), which is higher than what is considered the average in the literature (6–10 mg/mL in colostrum) [23]. The amount of human milk intake is critical since there are many other factors present that can account for the protective effect, including antibodies, oligosaccharides, lysozyme, and mucins, among others [3].

In a small case-control study of newborns <32 weeks, Trend et al. [21] found that infants with LOS consumed lower quantities of human LF, measured on days 7 and 21 of life, in comparison with newborns who did not develop LOS. However, this analysis did not consider the consumption of breastmilk prior to the development of sepsis; they measured consumption in general. Nevertheless, these results are in line with our findings: infants that develop sepsis have a lower intake of human LF.

To our knowledge, this is the first study to explore human LF intake and its relation with LOS, NEC, and death. This protection early in life may be related to the LF effect on: (1) modulation of bacterial growth in the gastrointestinal tract; (2) promotion of intestinal cell proliferation, differentiation, and maturation, which may decrease intestinal permeability and prevent bacterial translocation from the gut to the bloodstream; and (3) regulation of the host immune response. These protective effects, as demonstrated in vitro and in animal models using bovine- and human LF, have been extensively reviewed [5, 6] and are much more relevant in the premature infant who is at risk of infection, inflammation, and oxidative stress injuries [6].

In this study we demonstrated that human milk intake as a whole protects against infections and death in the first 8 weeks of life. Several previous studies have shown similar results. Furman et al. [24] demonstrated that a daily threshold of at least 50 mL/kg of maternal milk through week 4 of life was needed to decrease the rates of LOS in VLBW infants. In a prospective cohort study in 175 VLBW infants, Patel et al. [20] demonstrated that the intake of at least 25 mL/kg/day over the first 28 days of life was significantly associated with a decrease in sepsis. However, both studies, as recognized in their limitations, did not calculate human milk intake before the onset of sepsis, or exclude the infants with sepsis episodes during a certain time of human milk exposure, to avoid the potential effect of reverse causality. A well-designed study by Corpeleijn et al. [19] demonstrated that the consumption of colostrum in the first 5 days of life and higher percentages (>50%) of MOM intake over days 6–10 of life protected against sepsis, NEC, and/or death in the first 60 days of life in VLBW infants. The relevance of this study and ours is that both demonstrated that the consumption of MOM early in life has a protective effect against infection and death for a prolonged period, up to 2 months of life. Our study adds information on LF intake. Several research studies have suggested that the early postnatal period (first 14 days of life) is a critical period for feeding human milk to decrease the risk of sepsis and other morbidities, including NEC [1, 25] and even re-hospitalizations over the first year of life [26].

In our study we found that VLBW infants who did not develop an event had a daily human LF intake of around 200 mg/kg in the first 10 days of life. This information is relevant to extrapolate the ideal dosing of bovine LF supplementation in current clinical trials, which is not clearly defined. The ELFIN [15] study in the UK used a dose of 150 mg/kg of bovine LF, with no significant protective effect against LOS, suggesting that probably a higher dose is needed on top of the amount that neonates are already receiving from MOM. A recent study by Manzoni et al. [27] evaluated the effect of bovine LF supplementation from 2 previous clinical trials and compared the effect among infants receiving only formula and mixed feeds. This study suggested that bovine LF supplementation may have a benefit among infants who do not receive MOM, and that probably there is no advantage of giving more LF to infants who are already receiving good quantities of MOM.

This study has some limitations. First, we did not measure LF concentrations in milk each day; only one measurement per mother was used as a homogeneous value for the daily calculations of LF intake. Since LF concentrations are high in colostrum and then decrease over time (Fig. 1), we have probably overestimated the amount of LF intake in some infants and underestimated it in others. To control for this, we have included in the analysis the date of milk sample collection. Second, we used a non-randomized design for the exposure of interest (high dose of human LF intake); therefore, the observed associations may have arisen because of group differences in variables not measured or not correctly measured. It is possible, for example, that sicker infants – even without LOS/NEC – may have received less MOM in the first 10 days and will also have had a higher subsequent risk of LOS/NEC/death. We did not adjusted by a measure of illness severity in the first 10 days of life.

Despite these limitations, our study has several strengths and important implications. The main strengths are the number of infants enrolled in the study and the exclusion from the analysis of all infants with an event during the exposure period. For clinicians, the main implication is that the finding that feeding higher amounts of human LF is associated with less infection and death highlights the importance of promoting MOM intake in the early postnatal period, especially for infants at risk in the neonatal units. For researchers, the protective doses of human LF intake reported in this study may aid in calculating the best dose for future clinical trials of bovine LF supplementation or other related research.

We would like to thank all members of the NEOLACTO Research Group who conducted the initial clinical trial. We thank the pediatricians, study research nurses, and neonatal nurses from each hospital for their dedication and careful work in this project.

The study was approved by the institutional Ethical Committee of Universidad Peruana Cayetano Heredia. We used coded data without personal identifiers.

The authors have no potential conflicts of interest to declare.

This study was funded by the National Institute of Child Health and Human Development (NICHD), grant No. R01-HD067694.

T.J.O. conceptualized and designed the study, obtained funding, analyzed and interpreted data, and drafted the manuscript. She had full access to all of the data in the study and takes responsibility for data integrity and the accuracy of data analyses. K.M. and C.C. conceptualized and designed the study, carried out the statistical analyses, and analyzed and interpreted the data. J.Z. and S.B. conceptualized and designed the study, coordinated the study, and collected, analyzed, and interpreted the data. J.J. and V.C. conceptualized and designed the study, and analyzed and interpreted the data. All authors critically reviewed the manuscript for important intellectual content, approved the final manuscript as submitted, and agree to be accountable for all aspects of the work.

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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