Pasteurization of Mother's Own Milk for Preterm Infants Does Not Reduce the Incidence of Late-Onset Sepsis

Article (PDF Available)inNeonatology 103(3):169-175 · December 2012with89 Reads
DOI: 10.1159/000345419 · Source: PubMed
Abstract
Background: Feeding preterm infants human milk has a beneficial effect on the risk of late-onset sepsis (LOS). Due to lack of microbiological standards, practices such as pasteurization of mother's own milk differ widely among neonatal intensive care units worldwide. Objectives: To investigate whether pasteurization of mother's own milk for very-low-birth-weight (VLBW) infants influences the incidence and severity of infection-related outcomes. Methods: In this randomized controlled trial, preterm infants (gestational age <32 weeks and/or birth weight <1,500 g) received either raw or pasteurized mother's own milk during the first 8 weeks of life. The primary outcome was the incidence of proven LOS. A dose-response relation was verified, i.e. the dependence of the risk of sepsis on the actual and cumulative quantities of mother's own milk. Results: This study included 303 VLBW infants (mean birth weight: 1,276 g; mean gestational age: 29 weeks) whose baseline and nutritional characteristics were similar. The incidence of laboratory-confirmed sepsis was not statistically different in infants fed raw milk compared to infants who received pasteurized milk: 22/151 (0.15, CI: 0.08-0.20) and 31/152 (0.20, CI: 0.14-0.27), respectively (RR: 0.71; 95% CI: 0.43-1.17). A significant dose-response relation was observed between the adjusted quantity of enteral feeding and the risk of LOS, regardless of the type of feeding. Conclusion: For preterm infants, pasteurization of mother's own milk shows a trend towards an increase in infectious morbidity, although no statistical significance was reached. Practices should focus on collection, storage and labeling procedures to ensure the safety and quality of expressed milk.
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Original Paper
Neonatology 2013;103:170176
DOI: 10.1159/000345419
Pasteurization of Mothers Own Milk
for Preterm Infants Does Not Reduce
the Incidence of Late-Onset Sepsis
Veerle Cossey
a, b
Chris Vanhole
a
An Eerdekens
a
Maissa Rayyan
a
Steffen Fieuws
c
Annette Schuermans
b
a
Neonatal Intensive Care Unit and
b
Department of Hospital Hygiene and Infection Control, University Hospitals
Leuven, and
c
Interuniversity Centre for Biostatistics and Statistical Bioinformatics, Department of Public Health,
Leuven , Belgium
infants who received pasteurized milk: 22/151 (0.15, CI: 0.08–
0.20) and 31/152 (0.20, CI: 0.140.27), respectively (RR: 0.71;
95% CI: 0.43–1.17). A significant dose-response relation was
observed between the adjusted quantity of enteral feeding
and the risk of LOS, regardless of the type of feeding. Conclu-
sion: For preterm infants, pasteurization of mother’s own
milk shows a trend towards an increase in infectious morbid-
ity, although no statistical significance was reached. Practic-
es should focus on collection, storage and labeling proce-
dures to ensure the safety and quality of expressed milk.
Copyright © 2012 S. Karger AG, Basel
Background
As survival rates for preterm infants improve, more
attention is being focused on the quality of survival
through optimal nutritional management. Breast-feed-
ing or the use of mother’s own expressed milk is the gold
standard for all infants
[1] . Human milk benefits very-
low-birth-weight (VLBW) infants and lowers their risk
for late-onset sepsis (LOS)
[25] , which occurs in 1636%
of infants with a birth weight less than 1,500 g
[6, 7] . Strat-
egies for prevention are crucial for decreasing the burden
of infections in neonatal intensive care units (NICU), and
Key Words
Human milk Neonatal sepsis Randomized controlled
trial Nosocomial infections
Abstract
Background: Feeding preterm infants human milk has a
beneficial effect on the risk of late-onset sepsis (LOS). Due to
lack of microbiological standards, practices such as pasteur-
ization of mothers own milk differ widely among neonatal
intensive care units worldwide. Objectives: To investigate
whether pasteurization of mothers own milk for very-low-
birth-weight (VLBW) infants influences the incidence and se-
verity of infection-related outcomes. Methods: In this ran-
domized controlled trial, preterm infants (gestational age
! 32 weeks and/or birth weight ! 1,500 g) received either raw
or pasteurized mothers own milk during the first 8 weeks of
life. The primary outcome was the incidence of proven LOS.
A dose-response relation was verified, i.e. the dependence
of the risk of sepsis on the actual and cumulative quantities
of mother’s own milk. Results: This study included 303 VLBW
infants (mean birth weight: 1,276 g; mean gestational age: 29
weeks) whose baseline and nutritional characteristics were
similar. The incidence of laboratory-confirmed sepsis was
not statistically different in infants fed raw milk compared to
Received: June 15, 2012
Accepted after revision: October 25, 2012
Published online: December 20, 2012
Veerle Cossey, MD, PhD
Neonatal Intensive Care Unit
University Hospitals Leuven, Herestraat 49
BE–3000 Leuven (Belgium)
E-Mail veerle.cossey
@ uzleuven.be
© 2012 S. Karger AG, Basel
1661–7800/13/10330170$38.00/0
Accessible online at:
www.karger.com/neo
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Pasteurization of Mother’s Own Milk for
Preterm Infants
Neonatology 2013;103:170176
171
focus on hygiene measures and restrictive use of invasive
devices
[8, 9] .
The role of nutritional regimens in the occurrence of
LOS has not been studied extensively. The bioactive fac-
tors in human milk promote the development of a bal-
anced intestinal ecosystem and modulate innate and
adaptive immunity
[10] . However, human milk is not
sterile and can be a vehicle for commensal or pathogenic
microorganisms derived from the mother or the environ-
ment during collection, storage and handling of the milk
[11] . Organisms linked to human milk-induced infec-
tions include Staphylococcus aureus , group B streptococ-
ci, Escherichia coli , Serratia spp., Pseudomonas spp., Sal-
monella spp., HIV and cytomegalovirus
[1215] .
Good practices for expression, collection, transport,
storage and administration of human milk in neonatal
care have been developed
[16, 17] , but, as opposed to for-
mula milk, no microbiological quality standards are
available for expressed mother’s own milk. In order to
further neutralize any microbial contamination, addi-
tional steps such as bacteriological screening and heat
treatment of the milk can be considered, especially for
susceptible preterm infants. Pasteurization inactivates
potential pathogens, but the process negatively affects the
unique immunological and nutritional quality of the
milk.
In this study, we investigated whether pasteurization
of mother’s own milk for VLBW infants influences the
incidence and severity of infection-related outcomes dur-
ing their stay in the NICU. We hypothesized that short-
term infection-related benefits of human milk are de-
creased by the process of pasteurization.
M e t h o d s
Patient Enrolment
All patients born before 32 weeks of gestational age and/or
with a birth weight below 1,500 g admitted to the NICU of the
University Hospitals Leuven within 24 h of birth were eligible for
the study, except for infants who died within the first 24 h ( fig.1 ).
Infants whose mothers intended to breast-feed were randomly
assigned, using sequentially numbered and sealed envelopes, to
receive either raw or pasteurized mother’s own milk. The dura-
tion of the study was from birth to 8 weeks of age or to discharge
from the NICU, whichever occurred first. The need to ensure
proper handling of the milk precluded true blinding of the nurses;
the attending physicians were not aware of the intervention allo-
cation. The institutional review board approved the study and
informed consent was obtained.
Study Procedures
Infants who were assigned to pasteurization received own
mother’s milk, heated in sealed bottles at 62.5
° C for 30 min with
a Sterifeed S75 TES pasteurizer. Infants who were assigned to the
raw group received fresh or thawed milk from their own mother.
Raw milk containing any Gram-negative organisms, S. aureus or
enterococci, was temporarily withheld and replaced by formula
milk
[17] . If contamination persisted after maternal instructions
on expression and storage had been repeated, the milk was pas-
35 were excluded
admission >24 h of age (n = 30)
survival <24 h (n = 4)
no informed consent (n = 1)
434 patients were assessed
for eligibility
96 received exclusive
preterm formula milk
303 received human milk and
underwent randomization
152 were assigned to
pasteurized mother’s own milk
152 were included in the
analysis by intention-to-treat
151 were assigned to raw
mother’s own milk
151 were included in the
analysis by intention-to-treat
399 were enrolled
Fig. 1. Distribution of subjects.
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172
teurized. If maternal milk (MM) was insufficiently available, pre-
term formula was used as a supplement (PreNAN Nestlé Nutri-
tion, Nenatal , Nutricia). No donor milk was used.
Outcome Measures
The primary endpoint was the incidence of proven LOS, oc-
curring more than 48 h after birth, with growth of a pathogen or
coagulase-negative staphylococci (CoNS) cultured from blood,
combined with the acute onset of two or more predefined clinical
signs, and (only in case of growth of a CoNS isolate) at least one
laboratory parameter of systemic infection
[18] . A BacT/ALERT
microbial detection system (bioMérieux, Marcy l’Etoile, France)
was used.
Secondary endpoints were the incidence of clinical sepsis as-
sessed as an episode of antimicrobial treatment for at least 5 days
in the presence of clinical signs; infection site other than the
bloodstream; antibiotic utilization rate; NEC (necrotizing entero-
colitis) stages II and III according to modified Bell criteria; peri-
ventricular leukomalacia or intraventricular hemorrhage, exclud-
ing grade I bleeding; need for respiratory support; chronic lung
disease defined as the need for supplemental oxygen at 36 weeks
postmenstrual age; retinopathy of prematurity; length of NICU
stay; and in-NICU mortality. We compared the two study groups
with respect to nutritional variables as age at full enteral feeding
and weight gain.
Statistical Analyses
Retrospective original data indicated that the incidence of
LOS was 40% among preterm infants receiving formula milk. To
detect, with 80% power, an absolute decrease of 15% in LOS, 152
infants per group were needed based on a two-sided
2
test (with
set at 5%). The comparison between both groups was made on
an intent-to-treat basis; all randomized infants remained in their
group for the final analyses. Fisher’s exact test was used to com-
pare the proportion of infections between both groups, reporting
the crude event rate. To handle the presence of deaths without in-
fection, two other approaches were used: a comparison of the in-
fection rate on the subset of patients who were alive at discharge
or had an infection preceding the in-NICU death, and an analysis
of the time until infection, treating in-NICU death, or discharge
without infection as competing risks. A Cox regression model
with time-dependent covariates was used to verify the relation
between enteral feeding or MM and the risk of LOS. All reported
p values were two-sided and considered significant if smaller than
0.05. Analyses were performed using SAS software, version 9.2 of
the SAS System for Windows (2002, SAS Institute Inc.). Exact CIs
were obtained with StatXact-9.
R e s u l t s
Study Intervention
Between March 2006 and December 2010, 399 of 434
eligible infants were enrolled, of whom 303 infants (76%)
were initiated on human milk feeding and included in the
analysis ( fig.1 ). For 24 infants in the raw group, the milk
was pasteurized at a later stage (after 23 8 11 days) due
to persistent contamination with pathogens. There were
no differences in birth weight, gestation, Apgar and CRIB
score between the raw and pasteurized MM groups ( ta-
ble1 ).
Table 1. B aseline characteristics of study population
Variable Group raw MM
(n = 151)
Group pasteurized
MM (n = 152)
p value
Maternal factors, n (%)
Caesarean delivery
Prolonged rupture of membranes (>18 h)
Histologic chorioamnionitis
Use of antenatal steroids
Use of antenatal antibiotics
Outborn delivery
Multiple gestation
Infant factors
Birth weight, g
1
Gestational age, weeks
2
Male gender, %
Apgar score <7 at 5 min, n (%)
Small for gestational age (<P10), n (%)
CRIB score
2, 3
100 (65)
39 (25)
25 (16)
142 (94)
46 (30)
10 (6)
61 (40)
1,2918353
30 (28–31)
47
6 (4)
20 (13)
1 (0–2)
116 (76)
43 (28)
21 (13)
139 (92)
44 (29)
7 (4)
88 (57)
1,2708406
30 (28–31)
53
7 (5)
25 (16)
1 (0–3)
0.07
0.72
0.61
0.82
0.87
0.61
0.003
0.49
0.37
0.39
0.99
0.53
0.24
1
Mean 8 SD.
2
Median (IQR).
3
Scores on clinical risk index for babies (CRIB) range from 0 to 24 with
higher scores indicating a greater severity of illness.
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C l i n i c a l O u t c o m e s
Among 303 VLBW infants who received MM, 61 epi-
sodes of proven LOS occurred in 53 patients ( table 2 ).
Fewer patients in the raw milk group acquired laborato-
ry-confirmed sepsis compared to infants who received
pasteurized milk; 22 of 151 (0.15, CI: 0.08–0.20) and 31 of
152 (0.20, CI: 0.140.27), respectively (RR: 0.71; 95% CI:
0.43–1.17). Two septic episodes occurred in the raw MM
group after the switch to pasteurized milk. The age at on-
set of LOS was similar between the groups, with 72% of
the first episodes occurring between 7 and 21 days of age.
Clinical sepsis also occurred more in infants fed pasteur-
ized milk (RR: 0.76; 95% CI: 0.481.22). No differences
were noted between both groups for infections at other
sites or for use of antibiotics. The overall incidence of se-
vere NEC was 7.3%; all surgical cases occurred in infants
who received pasteurized MM at some time before the
onset of NEC. None of the deaths were related to infection
or NEC.
Of the 61 episodes of sepsis, 51 were due to CoNS, 9 to
S. aureus and 1 to Klebsiella oxytoca . Staphylococcus epi-
dermidis was the leading pathogen identified in 52% of
episodes in the raw MM group and 44% in the pasteur-
ized MM group, followed by Staphylococcus capitis (24
and 25%, respectively) and S. aureus (12 and 16%, respec-
tively). Of 473 samples of raw milk, 98.3% yielded bacte-
Table 2. C linical outcome variables by group of milk feeding
Variable Group raw
MM (n = 151)
Group pasteurized
MM (n = 152)
p
value
RR
(exact 95% CI)
Infection-related outcomes
Proven LOS, n (%)
Patients with 1 episode, n
Patients with >1 episode, n
Episodes, n
Day of onset of first episode
1
Clinical sepsis
Patients, n (%)
Episodes, n
Proven and/or clinical sepsis, n (%)
NEC stage ≥2, n (%)
Day of onset
1
Surgery for NEC, n
Proven LOS and/or NEC, n (%)
Infections at other sites, number of patients
Cerebrospinal fluid
Airway or lung
Urinary tract
Skin or joint
Antibiotic utilization rate
1, 2
Immunoglobulins for sepsis, n (%)
22 (15)
20
2
25
16 (9–26)
25 (16)
33
38 (25)
13 (8)
22 (17–31)
0
31 (20)
0
39
3
0
22 (10–40)
15 (10)
31 (20)
31
5
36
13 (9–22)
32 (21)
51
51 (33)
9 (5)
20 (13–23)
4
37 (24)
0
36
1
1
23 (13–42)
18 (12)
0.23
0.31
0.39
0.49
0.87
0.29
0.71
0.71 (0.44–1.17)
0.76 (0.48–1.22)
1.45 (0.65–3.26)
0.84 (0.55–1.29)
Other secondary outcomes
IVH/PVL, n (%)
Respiratory support, days
1
Chronic lung disease, n (%)
Steroids for chronic lung disease
ROP requiring surgery, n (%)
Length of NICU stay, days
1, 3
Death during study period, n (%)
Day of age
1
21 (13)
9 (4–25)
24 (16)
24 (16)
8 (5)
29 (19–56)
5 (3)
6 (5–10)
29 (19)
12 (5–29)
35 (23)
37 (24)
9 (6)
37 (23–64)
8 (5)
8 (5–23)
0.29
0.30
0.15
0.08
0.99
0.14
0.57
I VH = Intraventricular hemorrhage; PVL = periventricular leukomalacia; ROP = retinopathy of prematu-
rity.
1
Median (IQR).
2
Total antibiotic days/total patient days ! 100.
3
Excluding patients deceased during the
study period.
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rial isolates, mainly CoNS only (in 81% of samples with
growth). Postpasteurization samples showed no growth.
There were no significant differences between the two
study groups in the use of antibiotics, duration of respira-
tory support, incidence of intraventricular hemorrhage
or periventricular leukomalacia, or surgical retinopathy
of prematurity. Fewer patients in the raw MM group ac-
quired chronic lung disease (16 vs. 24%, p = 0.13). The
median duration of NICU hospitalization was 8 days
shorter in the raw MM group (p = 0.36).
Table 3. N utritional outcomes by groups of milk feeding
Variable Group raw MM
(n = 151)
Group pasteurized
MM (n = 152)
p value
Day of first MM feeding
1
Age achieved full enteral feeding, days
1
Birth weight regained, days
1
Weight gain, g/kg/day
2, 3
Enteral intake, ml/kg/day
2
Per day of hospitalization
Per day of enteral feeding
Mother’s own milk intake, ml/kg/day
2
Per day of hospitalization
Per day of MM feeding received
Per day of enteral feeding received
Cumulative intake, liter
Proportion of total enteral intake
1
Proportion with fortification
Central venous catheter use, days
1
Parenteral nutrition (full or partial), days
1
Intravenous lipids, days
1
Days without enteral feeding
1
Use of H2 antagonists, n (%)
2 (1–3)
17 (14–21)
11 (9–14)
20810
66833
77833
51833
64834
59835
2.0681.9
86 (61–95)
29 (18–40)
15 (11–20)
17 (13–26)
10 (6–17)
3 (2–6)
21 (14)
2 (2–3)
19 (15–24)
11 (8–14)
20811
70832
82833
56831
68833
64833
2.2981.7
88 (54–95)
41 (30–48)
16 (11–22)
18 (14–26)
12 (7–18)
3 (2–6)
18 (12)
0.78
0.17
0.51
0.26
0.27
0.25
0.19
0.22
0.17
0.27
0.20
0.32
0.34
0.42
0.30
0.51
0.73
1
Median (IQR).
2
Mean 8 SD.
3
Average daily increments for body weight for the period between the time
that birth weight was regained and discharge or death or age 57 days.
Table 4. R isk of proven LOS according to various quantifications of milk feeding
All subjects Group raw MM G roup pasteurized MM
p value hazard ratio (95% CI) p value hazard ratio (95% CI) p value hazard ratio (95% CI)
Actual quantity of enteral feeding
1
Actual quantity of maternal milk
1
Actual proportion of maternal milk
2
Cumulative quantity of enteral feeding
1
Cumulative quantity of maternal milk
1
Cumulative proportion of maternal milk
2
Maternal milk >50 ml/kg/day
3
<0.0001
0.0008
0.405
<0.0001
0.0001
0.371
0.283
0.85 (0.80–0.91)
0.89 (0.83–0.95)
0.98 (0.98–0.99)
0.99 (0.98–0.99)
0.67 (0.33–1.39)
0.0001
0.007
0.486
0.001
0.021
0.395
0.264
0.80 (0.72–0.90)
0.85 (0.76–0.96)
0.98 (0.97–0.99)
0.99 (0.98–0.99)
0.53 (0.17–1.62)
0.009
0.076
0.128
0.001
0.003
0.530
0.732
0.90 (0.83–0.97)
0.92 (0.85–1.01)
0.99 (0.98–0.99)
0.99 (0.98–0.99)
0.85 (0.33–2.18)
Ha zard ratios and 95% CI are obtained from a Cox regression model with the quantification of milk feeding treated as a time-de-
pendent covariate.
1
Effects are expressed per 10 ml/kg/day.
2
Categorized into levels 0, 0–0.25, 0.25–0.50, 0.50–0.75, 0.75–1 and 1.
3
In this quantifica-
tion, a child starts in the ‘low MM intake’ group and switches to the ‘high MM intake’ group as soon as the daily intake exceeds 50 ml/
kg.
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Table 3 presents outcomes related to nutrition and
growth. Among infants who reached full enteral feeding,
this was established at a median age of 17 (13–25) days in
the raw group and 19 (1425) days in the pasteurized
group (p = 0.17). No differences in growth were noted
between the two groups; birth weight was regained after
11 days, after that, weight was gained at 20 8 11 g/kg per
day. Human milk consumption was variable in both
groups with 14% (539) of total milk intake supplied as
artificial milk in the raw MM group and 12% (546) in
the pasteurized MM group.
Dose-Response Relation
A significant dose-response relation was observed be-
tween the adjusted (per kg) quantity of enteral feeding
provided and the risk of proven LOS ( table4 ). The same
observation was made for MM; infants receiving higher
amounts of MM had a lower risk of sepsis. For every dai-
ly increase of 10 ml per kg of MM, the risk of sepsis de-
creased by 12%. There was no evidence of a relation be-
tween the portion of MM, expressed as actual or cumu-
lative proportion of the total enteral intake, and the
infection risk, although the estimate for the effect was in
favor of MM.
Discussion
In this randomized trial, we evaluated the effects of
pasteurization of mother’s own milk, compared to un-
treated raw milk, on infection-related events in VLBW in-
fants during their NICU stay in the first 8 weeks of life.
The observed proven LOS rate was lower for infants re-
ceiving raw MM compared to pasteurized MM (RR: 0.71;
95% CI: 0.431.17); hence, enteral feeding with heat-treat-
ed MM increased the risk of proven LOS by 41%. A simi-
lar conclusion and relative risks (and 95% CI) are obtained
if other statistical approaches are used, taking into ac-
count the deaths without infection. Given the lower inci-
dence of LOS in the study groups compared to retrospec-
tive data, the study was insufficiently powered to detect a
clinically relevant difference for the primary outcome.
Other findings were a shorter NICU stay, by 8 days, in
the raw group compared to the group with pasteurized
MM, as well as the absence of surgical NEC and a ten-
dency for less chronic lung disease.
The findings of this study indicate that raw mother’s
own milk is at least equivalent to pasteurized milk with
respect to the risk of LOS, provided that the milk is col-
lected and handled according to the quality and safety
principles of HACCP. No other studies have identified ef-
fects of pasteurized versus raw mother’s own milk on in-
fection-related events, which makes this study unique in
its design. Most studies assessing the relation between
nutrition and infection in VLBW infants are observa-
tional cohort studies comparing MM with formula milk.
Only one randomized trial compared 243 extremely pre-
mature infants fed with pasteurized donor human milk
or preterm formula, both as substitutes for MM, and
failed to find a protective effect of donor milk on the com-
bined incidence of LOS and/or NEC compared to formu-
la, in contrast to exclusive mother’s own milk feeding,
given raw, which was protective for LOS
[9] .
Few observational studies in preterm infants have as-
sessed a possible dose-response relationship and a thresh-
old protective amount of MM
[19, 20] . In the current
study, an inverse relationship was noted between both the
actual or cumulative amount of enteral feeding an infant
received and the subsequent risk of LOS, showing a dose-
response effect. Nevertheless, LOS did not correlate sig-
nificantly with the proportion of MM to total intake, nei-
ther raw nor pasteurized, and no threshold for protection
against LOS could be identified for any type of milk.
From our data we can only conclude that the higher the
intake of enteral feeding, whether human or artificial
milk, the lower the incidence of infection. Obviously, no
causal relation can be established since the amount of en-
teral feeding might only be an inverse indicator of disease
severity or susceptibility to sepsis.
The increased rates of LOS associated with the use of
pasteurized MM may be explained by several mecha-
nisms. First, the process of pasteurization negatively af-
fects the immunological quality of the milk by partial
destruction of immunocomponents and partial loss of
bactericidal activity
[21, 22] . Second, we speculate that
early gut colonization might be affected if nonpathogen-
ic maternal bacteria and bifidogenic components in the
milk are destroyed by heat, leading to a more virulent in-
testinal microbiota and increasing the risk for systemic
infections by translocation of bacteria
[23, 24] .
In this study, no differences in weight gain or feeding
intolerance were found between VLBW infants fed pas-
teurized as compared to raw mother’s own milk. Our data
do not support the data reported in previous studies in
terms of slower weight gain with pasteurized milk
[9, 12,
25]
. This finding cannot be explained by the use of milk
fortifiers, which was not significantly different in both
groups.
There are some limitations to the current study. Com-
plete blinding of NICU providers for the type of milk was
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impossible due to different cold chain logistics. Also, the
sample size was not large enough to adequately assess the
effect of pasteurization of MM on morbidities that occur
at lower rates such as NEC or retinopathy of prematurity.
Finally, due to the realities of breast-feeding VLBW in-
fants with prolonged milk expression, the ideal model of
exclusive human milk feeding was not obtained.
Conclusion
Pasteurization of mother’s own milk given to VLBW
infants during their NICU hospitalization is an interven-
tion that does not improve infection-related outcomes
such as LOS. In view of the results of this study, it seems
appropriate not to include pasteurization when develop-
ing strategies aimed at reducing short-term infectious
morbidity. Attention to collection, storage and labeling
procedures to ensure the safety and quality of expressed
milk should be emphasized.
Acknowledgments
We are grateful to all the parents of the participating infants.
We thank the attending physicians, residents and nurses at the
NICU of the University Hospitals Leuven and all the personnel of
the lactation program and milk kitchen.
Disclosure Statement
No conflict of interest to declare.
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    • "This in-vitro finding might suggest that preterm infants fed pasteurized HM may be more susceptible to clinical bacterial infections and other morbidities than those fed raw milk. However, recent studies did not confirm this hypothesis [26,36]. "
    [Show abstract] [Hide abstract] ABSTRACT: Own mother's milk is the first choice in feeding preterm infants and provides multiple short- and long-term benefits. When it is unavailable, donor human milk is recommended as the first alternative. Donor milk undergoes processing (i.e. pasteurization) to reduce bacteriological and viral contaminants but influences its bioactive properties with potentially fewer benefits than raw milk. However, there is no clinical evidence of health benefit of raw compared to pasteurized human milk, and donor milk maintains documented advantages compared to formula. Nutrient content of donor and own mother's milk fails to meet the requirements of preterm infants. Adequate fortification is necessary to provide optimal growth. There are significant challenges in providing donor milk for premature infants; therefore, specific clinical guidelines for human milk banks and donor milk use in the neonatal intensive care unit should be applied and research should focus on innovative solutions to process human milk while preserving its immunological and nutritional components. In addition, milk banks are not the only instrument to collect, process and store donor milk but represent an excellent tool for breastfeeding promotion.
    Full-text · Article · Sep 2016
    • "BMderived leukocytes may aid in protecting infants from infection through normal protective functions such as phagocytosis and production of antimicrobial peptides, and have been found in the peripheral circulation and distant tissues of animal models after ingestion [10, 42], with observed effects on blood leukocyte populations in both animal and human studies43444546. However, it is unlikely that low consumption of leukocytes, independent of the many other protective functions of the soluble molecules in milk, is responsible for the increased infection risk in preterm infants fed PDHM and those consuming low BM volumes [1, 47]. Contrary to previous reports of increased leukocyte concentrations in BM in maternal or infant infections [27, 34] , we did not observe significant increases in absolute leukocyte concentration during infections in our study. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Extremely preterm infants are highly susceptible to bacterial infections but breast milk provides some protection. It is unknown if leukocyte numbers and subsets in milk differ between term and preterm breast milk. This study serially characterised leukocyte populations in breast milk of mothers of preterm and term infants using multicolour flow cytometry methods for extended differential leukocyte counts in blood. Methods Sixty mothers of extremely preterm (<28 weeks gestational age), very preterm (28–31 wk), and moderately preterm (32–36 wk), as well as term (37–41 wk) infants were recruited. Colostrum (d2–5), transitional (d8–12) and mature milk (d26–30) samples were collected, cells isolated, and leukocyte subsets analysed using flow cytometry. Results The major CD45+ leukocyte populations circulating in blood were also detectable in breast milk but at different frequencies. Progression of lactation was associated with decreasing CD45+ leukocyte concentration, as well as increases in the relative frequencies of neutrophils and immature granulocytes, and decreases in the relative frequencies of eosinophils, myeloid and B cell precursors, and CD16- monocytes. No differences were observed between preterm and term breast milk in leukocyte concentration, though minor differences between preterm groups in some leukocyte frequencies were observed. Conclusions Flow cytometry is a useful tool to identify and quantify leukocyte subsets in breast milk. The stage of lactation is associated with major changes in milk leukocyte composition in this population. Fresh preterm breast milk is not deficient in leukocytes, but shorter gestation may be associated with minor differences in leukocyte subset frequencies in preterm compared to term breast milk.
    Full-text · Article · Aug 2015
    • "Avoidance of tube feeding by earlier introduction of oral feeding and preventive strategies related to switching from tube feeding to oral feeding have been discussed earlier. Avoidance of pasteurization in the setting of mother's own milk seems a very reasonable option, when there is sufficient focus on collection, storage and labeling procedures to ensure the safety and quality of expressed milk [37]. Pasteurization does not only affect the lipid content, but also other characteristics, including bactericidal functions or functional elimination of lipase activity present in fresh human milk [38]. "
    [Show abstract] [Hide abstract] ABSTRACT: Deficient nutritional support and subsequent postnatal growth failure are major covariates of short- and long-term outcome in preterm neonates. Despite its relevance, extrauterine growth restriction (EUGR) is still prevalent, occurring in an important portion of extremely preterm infants. Lipids provide infants with most of their energy needs, but also cover specific supplies critical to growth, development and health. The use of human milk in preterm neonates results in practices, such as milk storage, pasteurization and administration by an infusion system. All of these pre-exposure manipulations significantly affect the final extent of lipid deposition in the intestinal track available for absorption, but the impact of tube feeding is the most significant. Strategies to shift earlier to oral feeding are available, while adaptations of the infusion systems (inversion, variable flow) have only more recently been shown to be effective in "in vitro", but not yet in "in vivo" settings. Pre-exposure-related issues for drugs and nutritional compounds show similarities. Therefore, we suggest that the available practices for "in vitro" drug evaluations should also be considered in feeding strategies to further reduce pre-exposure losses as a strategy to improve the nutritional status and outcome of preterm neonates.
    Full-text · Article · Aug 2015
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