European Journal of Clinical Nutrition (2006) 60, 756–762
& 2006 Nature Publishing Group All rights reserved 0954-3007/06 $30.00
www.nature.com/ejcn
ORIGINAL ARTICLE
Fat-soluble vitamins in breast-fed preterm and term
infants
C Henriksen1, IB Helland2, A Rønnestad2, M Grønn2, PO Iversen1 and CA Drevon1
1
Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway and 2Department of Pediatrics,
Rikshospitalet University Hospital, Oslo, Norway
Objective: To examine the supply and status of fat-soluble vitamins in very low birth weight (VLBW) infants compared to a
reference group of normal birth weight (NBW) infants.
Design: A longitudinal study of VLBW infants in the early neonatal period. Blood samples were drawn at 1 week of age and at
discharge from hospital. Plasma was analyzed for the fat-soluble vitamins: retinol, 25-OH-vitamin D, a-tocopherol and
phylloquinone (vitamin K1) using high-performance liquid chromatography.
Subjects: A total of 40 VLBW infants were included in the study. A reference group of 33 NBW infants was randomly selected
from one of our previous studies.
Results: The VLBW infants received fortified human milk, and daily oral vitamin supplement (Multibionta). In VLBW infants,
plasma retinol concentrations decreased and plasma 25-OH-vitamin D increased during the study period. VLBW infants had
significantly lower plasma retinol (0.3 vs 0.7 mM) and higher plasma 25-OH-vitamin D (166 vs 25 nM) at discharge compared to
NBW infants. Plasma phylloquinone concentration in VLBW infants was very high (53 ng/ml) at one week of age, especially in
the youngest infants (192 ng/ml), but decreased rapidly during the study period resulting in low/normal plasma concentrations
(0.9 ng/ml) at discharge.
Conclusions: We observed alterations in plasma concentration of retinol and 25-OH-vitamin D in VLBW infants in the early
neonatal period, resulting in marked differences between VLBW at discharge and NBW. Further trials are needed to evaluate
whether changes in vitamin supplementation may improve clinical outcome in VLBW infants.
Sponsorship: Norwegian Foundation for Health and Rehabilitation, the Johan Throne Holst Foundation for Nutrition Research
and the Research Council of Norway.
European Journal of Clinical Nutrition (2006) 60, 756–762. doi:10.1038/sj.ejcn.1602379; published online 1 February 2006
Keywords: very low birth weight (VLBW) infants; vitamin A; vitamin D; vitamin E; vitamin K
Introduction
Deficiency of fat-soluble vitamins may lead to serious health
problems during fetal development as well as after birth.
Correspondence: Professor CA Drevon, Department of Nutrition, Institute of
Basic Medical Sciences, University of Oslo, POB 1046 Blindern, Oslo 0316,
Norway. E-mail: [email protected]
Guarantor: CA Drevon.
Contributors: CH had primary responsiblity for protocol development, patient
enrollment, data analysis and writing the manuscript. AR and MG participated
in the development of the protocol and analytical framework for the study and
contributed to the writing of the manuscript. IBH contributed in the same ways
as AR and MG and was responsible for patient enrollment of NBW infants. POI
and CAD supervised the design and execution of the study, performed the final
data analyses and contributed to the writing of the manuscript.
Received 14 June 2005; revised 14 October 2005; accepted 9 November
2005; published online 1 February 2006
Metabolites of fat-soluble vitamins are important ligands
for several transcription factors. Retinoic acid is necessary
for regulation of cell proliferation and differentiation.
Deficiency of vitamin A may promote chronic lung disease,
and increased susceptibility to infections and xerophthalmia
(Shenai, 1999). Vitamin D has important functions in
calcium- and bone homeostasis and deficiency may lead to
impaired bone mineralization and eventually rickets, in
addition to altered immune responses (Shils, 1999). Vitamin
E acts as an antioxidant, and deficiency may cause hemolytic
anemia and adversely affect development of the central
nervous system in preterm infants (Azzi and Stocker, 2000;
Brion et al., 2003). Vitamin K is necessary for carboxylation
of proteins that are important in blood coagulation and bone
formation, and deficiency may cause neonatal hemorrhage
(Saxena et al., 2001).
Fat-soluble vitamins
C Henriksen et al
757
Compared to healthy newborns, premature infants
have low plasma concentration of retinol, 25-hydroxyvitamin D and vitamin E at birth, reflecting that fetal
accumulation of these vitamins mainly takes place in the last
trimester of pregnancy (Haga and Lunde, 1978; Shenai et al.,
1981; Baydas et al., 2002). Plasma vitamin K levels are low at
birth in very low birth weight (VLBW ¼ birth weight
o1500 g) as well as normal birth weight (NBW ¼ birth
weight 42500 g) infants (Greer et al., 1988; Kumar et al.,
2001). Human milk is the preferred nutritional source
in enteral feeding of preterm infants (American Academy
of Pediatrics, 1998). However, the concentration of
fat-soluble vitamins in human milk is low, compared to
the recommended intake, and VLBW infants need
supplementation (Greer, 2001). Prophylactic vitamin supplementation is common, but the dosage and route
of administration vary markedly (American Academy of
Pediatrics, 1998; Shaw and Lawson, 2001; Hey, 2003).
Most studies of fat-soluble vitamins have been conducted
in formula-fed infants. Little is known about the status
of fat-soluble vitamins among breast-fed premature
infants. Delvin et al. (2005) reported that oral vitamin
supplementation resulted in similar plasma concentrations
of these vitamins in breast and formula-fed infants
(gestational age 33.5 weeks). The present study is the first
to describe intakes and plasma concentrations for all four
fat-soluble vitamins in VLBW infants (gestational age 29
weeks), compared to a reference group of NBW infants.
Owing to sensitive and advanced high-performance liquid
chromatography (HPLC) we have been able to monitor all
the fat-soluble vitamins in plasma samples from even the
smallest infants.
Methods
Patients
Fifty subsequent VLBW (birth weight o1500 g) infants
born between April and October 2002 at Rikshospitalet
University Hospital, Buskerud Hospital and Vestfold
Hospital in Norway, were eligible for the study. Infants
with major congenital abnormalities were not included,
and those who developed cerebral hemorrhage (grade 3 or 4)
as determined by ultrasound, were excluded from the
study. Written informed consent was obtained from the
parents and the study was approved by the Regional
Ethics Committee. A reference group of 33 NBW (birth
weight 42500 g, gestational age 437 weeks) infants
at 4 weeks of age was randomly selected from one of
our previous studies. The mothers of the NBW infants
received vitamin-supplemented oil (1.2 mg vitamin A,
10 mg vitamin D and 14 mg vitamin E per day) from
week 18 during pregnancy until 3 months after delivery,
in accordance with current Norwegian recommendations
(Helland et al., 2003).
Dietary intake
Dietary intake of VLBW infants during the neonatal period
was estimated from parenteral nutrition, human milk,
formulas and oral supplements. The vitamin contents of
commercially available products were obtained from the
manufacturers. Vitamin intake from human milk was
calculated using the Norwegian food composition table,
and other sources (Bolisetty et al., 1998). All VLBW infants
were given 0.5 mg (i.m.) vitamin K1 within 2 h after birth.
Minimal enteral feeding with human milk was started as
soon as possible, and the amount of parenteral feeding was
reduced as the intake of human milk gradually increased.
When the infants achieved an enteral intake of 100 ml/kg,
the human milk was fortified with proteins and minerals
(Presemps Semper AB, Stockholm, Sweden). All VLBW
infants received oral vitamin supplement (Multibionta
Trophen Merck, Darmstadt, Germany) containing 12.5 mg
of vitamin D, 750 mg of vitamin A (retinylpalmitate) and
2 mg of vitamin E (a-tocopherol). Infants on parenteral
nutrition (n ¼ 10) received 1 ml/kg/day of Vitalipid (Vitalipid, Kabi Pharmacia) and 0.5 mg vitamin K1 every third day.
Most VLBW infants (n ¼ 27) received one additional daily
dose of 15 mg vitamin E from birth to 32 weeks of gestational
age. At discharge, 60% of the VLBW infant was breast-fed,
and the remaining changed from donor human milk to term
formula the last week before discharge.
All NBW infants were breast-fed during the study period.
Apart from 1.0 mg (i.m.) vitamin K1 at birth, NBW infants
received no vitamin supplement during the first 4 weeks of
life.
Blood sampling and analyses
Blood samples (1 ml) from the VLBW infants were obtained
in EDTA containers at 1 week of age and at discharge from
the hospital. Blood samples were obtained from the NBW
infants, at 4 weeks of age.
The blood samples were centrifuged, and plasma was
stored at 801C until further analyses. The plasma concentration of retinol was used as an indicator of vitamin A
status, and 25-OH-vitamin D was used as a marker of vitamin
D status. We also determined the major form of vitamin E (atocopherol) and vitamin K1 (phylloquinone). The analyses
were performed with HPLC on a Hewlett Packard 1100 liquid
chromatograph (Agilent Technologies, Palo Alta, CA, USA)
with very high sensitivity. For detection of retinol, the
method is linear at 0.1–10 mM and the lower limit of
detection is 10 nM. The intra-assay coefficient of variation
(CV) is 4.9–5.8%, using known standards during our
analyses. For 25-OH-vitamin D, the method is linear at 5–
400 nM and the lower limit of detection is 1–4 nM. CV is 5.2–
5.8%. For tocopherol, the method is linear at 1–200 mM and
the lower limit of detection is 10 nM. CV is 4.6–4.8%. For
phylloquinone, the method is linear at 0.05–4 ng/ml, and
the lower limit of detection was 0.01 ng/ml CV is 7.8–10%.
European Journal of Clinical Nutrition
Fat-soluble vitamins
C Henriksen et al
758
Statistics
Data are presented as medians with 25 and 75 percentiles.
Differences between groups were tested by the Mann–
Whitney U-test for continuous variables and Fisher’s exact
test for categorical variables. Statistical significance was
defined as a P-value o0.05.
Results
Patient characteristics
Fifty VLBW infants were initially eligible to participate in
the study. Seven infants were not included due to lack
of parental consent (n ¼ 2), transfer to another hospital
(n ¼ 3), neonatal death (n ¼ 1) or early discharge (n ¼ 1). Two
infants were excluded due to serious cerebral hemorrhage
and one withdrew during the study. Thus, 40 infants
participated in the study. Blood samples at 1 week of age
were not taken if the infant had received blood transfusion
(n ¼ 6). Blood samples were obtained from 32 (80%) of the
infants one week after birth and from 26 (65%) infants at
discharge. The median post-conceptional age at discharge
was 37 weeks (35–40). There were no statistical differences
in maternal age, birth weight or gestational age between
participants and non-participants in the VLBW group (data
not shown). The mothers in the NBW group had longer
education and smoked less than the mothers in the VLBW
group (Table 1). Among the mother in the VLBW group, 21%
reported daily smoking, 18% smoked from time to time and
61% were non-smokers.
Intake and plasma concentration of fat-soluble vitamins
Vitamin A: The main source of vitamin A in VLBW infants
was supplements, and the total vitamin A intake increased
steadily during the study period (Figure 1a). Median plasma
retinol concentration declined during the study period
(P ¼ 0.04) in VLBW infants (Figure 1b). Plasma retinol
concentrations in VLBW infants at discharge were significantly lower than for NBW infants at 4 weeks of age (Table 2).
Vitamin D: The main source of vitamin D in VLBW infants
was supplements, and the total vitamin D intake increased
steadily during the study period (Figure 2a). Plasma 25-OHvitamin D concentration increased (Po0.001) in VLBW
infants (Figure 2b). At discharge VLBW infants had significantly higher concentration of 25-OH-vitamin D than NBWs
at 4 weeks of age (Table 2).
Vitamin E: The main source of vitamin E in VLBW infants
was supplements, and the total intake declined after 32th
gestational week (Figure 3a). Plasma concentration of atocopherol decreased in VLBW infants during the study
(Figure 3b, Table 2). There was no significant difference
between plasma concentration of a-tocopherol in VLBW at
discharge and NBW infants at 4 weeks of age (Table 2).
Vitamin K: The main source of vitamin K was from
supplements, and the total intake declined during the study
period (Figure 4a). In infants who changed from donor milk
Table 1 Characteristics of mothers and infants
Mothers
Maternal age (years)
Education (%)
o10 years
10–12 years
412 years
Non-smokers (%)
Infants
Weight (g)
Length (cm)
Gestational length (weeks)
Small for gestational age (%)
Head circumference (cm)
Cesarean section (%)
Multiple gestations (%)
Apgar score 1 min
Apgar score 5 min
N-CPAPb (days)
Phototherapy (days)
Antibiotic treatment (days)
VLBW (n ¼ 40)
NBW (n ¼ 33)
P-value a
31 (26–35)
29 (26–31)
NS
8
61
31
61
9
25
66
94
1 115 (774–1 372)
37 (27–42)
29 (27–31)
15
26 (24–28)
75
30
6 (4–8)
8 (7–9)
13 (1–32)
1 (0–3)
7 (0–25)
3 710 (3 280–4 064)
51 (46–56)
40 (39–41)
3
36 (35–36)
21
0
8 (8–9)
9 (8–9)
Not examined
Not examined
Not examined
Data are presented as medians (25–75 percentile) or frequencies (%).
a
VLBW are compared to NBW group by the Mann–Whitney test or Fisher’s exact test, NS ¼ not significant.
b
Nasal continuous positive airway pressure.
European Journal of Clinical Nutrition
0.007
0.002
o 0.001
o 0.001
o 0.001
0.005
o 0.001
o 0.001
o 0.001
o0.001
NS
Fat-soluble vitamins
C Henriksen et al
759
Human milk
Formula
Parenteral
Table 2 Plasma concentration of retinol, a-tocopherol, 25-OH-Vitamin
D and phylloquinone
VLBW (n ¼ 32) a
1000
Supply of vitamin A (µg/day)
a
Suplements
900
Retinol (mM)
One week
Discharge/4 weeks
800
700
600
500
0.72 (0.62–0.86) o0.001
400
300
200
0
25 26-27 28-29 30-31 32-33 34-35 36-37 >38
a-Tocopherol (mM)
1 week
Discharge/4 weeks
35.0 (22.0–63.3)
23.0 (16.0–27.0)
22.6 (19.3–25.8)
NS
Phylloquinone (ng/ml)
1 week
Discharge/4 weeks
53.0 (18.2–179.4)
0.9 (0.4–1.5)
0.3 (0.2–0.5)
o0.001
Gestational age (weeks)
1.4
1.2
Plasma retinol (µM)
P-value b
24-OH-vitamin D (nM)
1 week
42.0 (26.0–89.0)
Discharge/4 weeks 166.0 (125.0–209.0) 25.0 (21.4–38.8) o0.001
100
b
0.50 (0.40–0.89)
0.30 (0.27–0.45)
NBW (n ¼ 32)
One week
Discharge
Data are presented as medians (25–75 percentile).
a
At discharge: n ¼ 26.
b
VLBW are compared to NBW group by the Mann–Whitney test, NS ¼ not
significant.
1
vitamins between breast-fed and non-breast-fed VLBW
infants at discharge (data not shown).
0.8
0.6
0.4
Discussion
0.2
The most striking finding in our study was the changes in
plasma concentration of retinol and 25-OH-vitamin D in
VLBW infants in the neonatal period, resulting in marked
differences between VLBW at discharge and NBW at 4 weeks
of age.
The decline in plasma retinol concentration in VLBW
infants may be of clinical importance because there is an
association between retinol status and the risk for developing
chronic lung disease (Hustead et al., 1984; Shenai et al., 1985;
Chabra et al., 1994; Inder et al., 1998). The optimal plasma
retinol concentration for newborn infants is not known.
Applying 0.7 mM plasma retinol as lower reference limit (de
Pee and Dary, 2002), all VLBW infants and 47% of the NBW
infants were deficient at discharge and 4 weeks after birth,
respectively. The observed intake of vitamin A in the VLBW
group was 2–3 times higher than the NBW infants. The low
plasma retinol levels at discharge might be explained by
higher needs and/or impaired absorption in the VLBW
group. The oral supplement contains retinylester, which
has to be hydrolyzed prior to absorption (Harrison and
Hussain, 2001), and possibly the involved enzymes have
reduced activity in VLBW infants. Low-fat intake and lack of
bile salts may further reduce bioavailability (Shils, 1999).
This is in accordance with results showing that oral
supplementation of 1500 mg retinol/day was inadequate for
obtaining optimal serum retinol concentration in very
preterm infants (Wardle et al., 2001), and further supported
by the observation that i.m. administration of vitamin A
0
24 26 28 30 32 34 36 38 40 42 44 46 48 50
Gestational age (weeks)
Figure 1 (a) Daily supply of vitamin A to VLBW infants is presented
as means (bars) at different gestational ages. (b) Plasma concentration of retinol in VLBW infants is presented as individual values at
different gestational ages. Blood samples were taken at 1 week of
age and at discharge.
to formula, the intake of vitamin K increased prior to
discharge. For infants receiving human milk, the intake of
vitamin K remained low during the rest of the study period.
Plasma concentration of phylloquinone was markedly
elevated at 1 week of age (Figure 4b), with considerable
individual variation. VLBW infants born at gestational age
o28 weeks had much higher plasma phylloquinone levels
than infants with gestational age 428 weeks (191.5 vs
19.3 ng/ml, P ¼ 0.005) one week after birth. VLBW infants on
parenteral nutrition had higher plasma concentrations of
phylloquinone than infants on enteral nutrition at similar
age (P ¼ 0.007). Plasma phylloquinone levels were low in
both groups at discharge/4 weeks age (Table 2).
All the NBW infants were breast-fed, but only 60% of the
VLBW infants were breast-fed at discharge. However, VLBW
infants had received mainly human milk during the study
period, and there were no significant difference in plasma
European Journal of Clinical Nutrition
Fat-soluble vitamins
C Henriksen et al
760
a
Human milk
Supplements
Human milk
Formula
Parenteral
Formula
Parenteral
a
Supply of vitamin E (mg/day)
Supply of vitamin D (µg/day)
16
Supplements
14
12
10
8
6
4
2
14
12
10
8
6
4
2
0
0
25
25 26-27 28-29 30-31 32-33 34-35 36-37 >38
Gestational age (weeks)
b
400
300
250
200
150
160
140
Plasma tocpherol (µM)
Plasma 25(OH)D (nM)
Gestational age (weeks)
b
One week
Discharge
350
26-27 28-29 30-31 32-33 34-35 36-37 >38
One week
Discharge
120
100
80
60
40
100
20
50
0
0
24 26 28 30 32 34 36 38 40 42 44 46 48 50
24 26 28 30 32 34 36 38 40 42 44 46 48 50
Gestational age (weeks)
Figure 2 (a) Daily supply of vitamin D to VLBW infants is presented
as means (bars) at different gestational ages. (b) Plasma concentration of 25-OH-vitamin D in VLBW infants is presented as individual
values at different gestational ages. Blood samples were taken at 1
week of age and at discharge.
normalizes serum retinol concentration, and decreases the
risk of death, chronic lung disease and oxygen requirement
in preterm infants (Darlow and Graham, 2002). However,
i.m. administration of vitamin A in very preterm infants is
not generally accepted, and oral administration would be
preferable.
A rapid increase in plasma 25-OH-vitamin D was observed
during the neonatal period, suggesting that a daily supplement of 12.5 mg may be too high. This is in contrast to
previous studies (Markestad et al., 1984; Backstrom et al.,
1999; Delvin et al., 2005), although our study included
smaller and more immature infants. Excessive intake of
vitamin D may lead to hypercalcemia and calcification of
soft tissues. Serum 25-OH-vitamin D concentration 4220 nM
is associated with hypercalcemia in adults (Vieth, 1999). Six
infants (22%) in the present study had 25-OH-vitamin D
levels 4220 nM at discharge, but no signs of hypercalcemia
European Journal of Clinical Nutrition
Gestational age (weeks)
Figure 3 (a) Daily supply of vitamin E to VLBW infants is presented
as means (bars) at different gestational ages. (b) Plasma concentration of alfa-tocopherol in VLBW infants is presented as individual
values at different gestational ages. Blood samples were taken at 1
week of age and at discharge.
were observed. The recommended daily dose of vitamin D
remains controversial and ranges between 4 and 25 mg/day
(Committee on Nutrition of the Preterm Infant, 1987;
American Academy of Pediatrics, 1998). Our results indicate
that a supplement of 12.5 mg/day is too high. In NBW
infants, the plasma concentration of 25-OH-vitamin D was
low at 4 weeks of life. This is expected due to the low vitamin
D concentration in human milk and lack of exposure to
sunlight at our Northern latitude. Our observation is in
accordance with the present Norwegian recommendations
of vitamin D supplementation to breast-fed infants from 4
weeks of age.
Plasma a-tocopherol levels were within the reference range
(14–50 mM) at discharge, except for two infants, who did not
receive additional vitamin E supplement. The recommended
daily dose of vitamin E varies between 6 and 12 mg/kg.
Although controversial, very high (pharmacological) doses
Fat-soluble vitamins
C Henriksen et al
761
a
Supplements
Human milk
Formula
Parenteral
Supply of vitamin K (µg/day)
70
60
50
40
30
20
10
0
25
26-27 28-29 30-31 32-33 34-35 36-37 >38
Gestational age (weeks)
Plasma phylloquinone (ng/ml)
b
10000
One week
Discharge
1000
100
10
1
0.1
24 26 28 30 32 34 36 38 40 42 44 46 48 50
Gestational age (weeks)
Figure 4 (a) Daily supply of vitamin K to VLBW infants are
presented as means (bars) at different gestational ages. (b) Plasma
concentration of phylloquinone in VLBW infants is presented as
individual values at different gestational ages. Blood samples were
taken at 1 week of age and at discharge.
of vitamin E have been proposed as an antioxidant to limit
retinopathy, cerebral hemorrhage, hemolytic anemia and
chronic lung disease with sepsis as a potential toxic side
effect (Brion et al., 2003). High-dose parenteral vitamin E
supplementation or serum levels 480 mM are not recommended (Brion et al., 2003). In the present study, four (13%)
of VLBW infants in contrast to none of the NBW infants had
a-tocopherol concentrations 480 mM.
Plasma vitamin K1 in VLBW was very high at 1 week of age
compared to earlier studies in healthy newborns (Shearer
et al., 1982; Greer et al., 1988) and in preterm infants (Kumar
et al., 2001; Costakos et al., 2003). Several authors, although
not confirmed in randomized studies, have suggested
deleterious side effects from high vitamin K levels such as
childhood leukemia and hepatoblastoma (Roman et al.,
2002). At present, it is not known whether high plasma
vitamin K concentration in the neonatal period increases
disease risks. However, this uncertainty should enhance
attention of vitamin K supplementation in VLBW infants.
Vitamin K1 was low at discharge in breast-fed VLBW
infants (0.7 ng/ml) as well as in NBW infants (0.3 ng/ml).
Greer et al. (Greer, 1999) reported that plasma phylloquinone concentrations in infants fed human milk were low
(o0.25 ng/ml) throughout the first 6 months of life
compared to formula-fed infants (4.39–5.99 ng/ml). Reduced
bone density is reported in preterm infants (Faerk et al.,
2000), and potentially low plasma vitamin K levels in breastfed, preterm infants may be a contributing factor (Weber,
2001).
The VLBW and NBW infants differed in gestational age,
birth weight, vitamin intake from supplements, and frequency of smoking during pregnancy among mothers.
With our present design, we cannot separate the effect of
prematurity from the effect of supplements. Smoking may
also reduce the content of some vitamins in human milk, but
most mothers quitted smoking during breastfeeding periods,
and therefore can probably not explain the observed
differences.
We compared VLBW infants at discharge to NBW infants.
VLBW infants had higher chronological age (8 vs 4 weeks),
but lower post-conceptional age (37 vs 44 weeks) compared
to the NBW infants. Choice of sampling time is a general
problem when comparing VLBW and NBW infants, and
similarity of both chronological age and post-conception age
are obviously not possible. The choice of sampling time has
probably not affected our conclusions because most fatsoluble vitamins, except vitamin D, are stable in NBW
infants in the early neonatal period.
In conclusion, the availability of very sensitive methods
for measuring concentrations of fat-soluble vitamins has
made it feasible to examine these vitamins in small plasma
samples from preterm infants. VLBW infants had significantly lower plasma retinol and higher plasma 25-OHvitamin D levels at discharge as compared to NBW infants.
There were no significant differences between plasma atocopherol levels in the two groups. Plasma phylloquinone
levels in VLBW infants were extremely high at 1 week of age,
especially in infants with gestational age below 28 weeks.
However, plasma concentrations of phylloquinone levels
were low in both groups at discharge/4 weeks of age. We
suggest that plasma concentrations of fat-soluble vitamins
should be monitored in VLBW infants to individually adjust
supplementation. Further trials are needed to evaluate
whether changes in vitamin supplementation may improve
clinical outcome in VLBW infants.
Acknowledgements
We thank Drs Per Arne Tølløfsrud, Rønnaug Solberg and Alf
Meberg for their participation in the study. We also thank
the staff at Rikshospitalet University Hospital, bioengineer
Louise Tunge and her colleagues for collecting blood samples
European Journal of Clinical Nutrition
Fat-soluble vitamins
C Henriksen et al
762
from the infants. The study was financially supported by the
Norwegian Foundation for Health and Rehabilitation, the
Johan Throne Holst Foundation for Nutrition Research and
the Research Council of Norway.
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