Nutrition 22 (2006) 731–737

www.elsevier.com/locate/nut
Applied nutritional investigation

Docosahexaenoic acid administered in the acute phase protects the

nutritional status of septic neonates
Mardya López-Alarcón, M.D., Ph.D.a,*, Mariela Bernabe-García, M.Sc.a,
Martha Del Prado, Ph.D.a, Dolores Rivera, R.D.a, Gabriela Ruiz, R.D.a,
Jorge Maldonado, B.Chem.a, and Raúl Villegas, M.D.b
a
Medical Nutrition Research Unit, Pediatric Hospital, Centro Médico Nacional “Siglo XXI,” Mexican Institute of Social Security, Mexico City, Mexico
b
Neonatal Intensive Care Unit, Pediatric Hospital, Centro Médico Nacional “Siglo XXI,” Mexican Institute of Social Security, Mexico City, Mexico

Manuscript received June 29, 2005; accepted April 7, 2006.

Abstract Objective: We tested the hypothesis of whether a pharmacologic, orogastric dose of docosahexae-
noic acid (DHA) administered during the acute phase of sepsis protects the nutritional status of
neonates.
Methods: A randomized, placebo-controlled trial was conducted. Neonates who developed sepsis
after a surgical procedure were randomly assigned to receive daily 100 mg of DHA or 100 mg of
olive oil as placebo for 14 d. At selection, illness severity was evaluated and a blood sample was
obtained to measure erythrocyte fatty acid composition. Energy intake and type of feeding were
recorded daily. Body composition was also determined at selection and after 14 d of follow-up with
the deuterium dilution technique. Body composition differences between d 14 and baseline were
calculated and compared between groups. Confounders were analyzed in a multiple regression
model.
Results: In all, 16 DHA and 11 placebo cases were followed up. Both groups showed an increase
in length and head circumference, but length gain tended to be greater in neonates with DHA (P ⫽
0.07). The DHA group presented increases in body mass (50 g, P ⫽ 0.03) and fat mass (70 g, P ⫽
0.03), whereas infants in the placebo group did not show an increase in any body composition
components. Gain in fat mass was positively related with the DHA of erythrocytes and whether or
not infants received DHA.
Conclusions: Orogastric DHA administered in the acute phase of infection likely protects the
nutritional status of neonates with sepsis. © 2006 Elsevier Inc. All rights reserved.

Keywords: Docosahexaenoic acid; Body composition; Sepsis; Neonates

The antiinflammatory properties of ␻-3 polyunsaturated
fatty acids (PUFA) are widely recognized. Animal and hu-
man studies have reported beneficial effects of ␻-3 PUFA
supplementation in several inflammatory conditions such as
rheumatoid arthritis, psoriasis, ulcerative colitis, and sys-
temic erythematous lupus [1–5]. The antiinflammatory
properties of ␻-3 PUFA are partially explained by their
This investigation was supported by a grant from the Consejo Nacional
para la Ciencia y Tecnología (CONACYT), Mexico, No. 7275 (to M.L.A.).
* Corresponding author. Tel.: ⫹52-55-5627-6944; fax: ⫹52-55-5627-
6944.
E-mail address: marsau2@prodigy.net.mx (M. López-Alarcón).
effects on eicosanoid physiology because eicosanoids de-
rived from these fatty acids are less potent than those de-
rived from ␻-6 PUFA. In addition, ␻-3 PUFA seemed to
decrease cytokine synthesis [5,6].
The proinflammatory cytokines interleukin-1␤, interleu-
kin-6, and tumor necrosis factor-␣ are responsible for most
of the catabolic effects of infection because these cytokines
act in concert by increasing resting energy expenditure and
glucose oxidation, decreasing fatty acid uptake by adipo-
cytes, and mobilizing muscle amino acids to produce he-
patic acute-phase proteins [7,8]. The net result of these
metabolic alterations is an excessive catabolism of sub-
strates and, secondarily, nutrition deterioration.

0899-9007/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.nut.2006.04.002
732 M. López-Alarcón et al. / Nutrition 22 (2006) 731–737
Thus, individuals who have inflammatory diseases are at
high risk of nutrition deterioration as a result of the second-
ary effects of cytokines on metabolism. Such is the case of
sepsis, a condition characterized by an uncontrolled inflam-
matory response and excessive production of cytokines [9].
When sepsis occurs in young children, the effect is more
devastating because nutrition deterioration impairs the ca-
pacity of the infant to respond to infection and places the
infant at a higher risk of mortality.
Most of the studies that report an antiinflammatory effect
of ␻-3 PUFA supplementation have administered these ␻-3
fatty acids for long periods of time, i.e., the fatty acid is
administered for 4 or 8 wk and the response is evaluated by
an infectious challenge, in vitro, at the end of the supple-
mentation period. This delayed response is understandable
because ␻-3 fatty acids need to be incorporated into cell
membranes to be available at the time of infection. How-
ever, because severe infections are characterized by an acute
phase of rapid leukocyte proliferation, we hypothesized that
the administration of an ␻-3 fatty acid such as docosahexae-
noic acid (DHA) in the acute phase of infection facilitates
its incorporation into leukocyte membranes. In conse-
quence, it may attenuate the deleterious effect of infection
on the nutritional status of neonates with sepsis.
Short-term changes in the nutritional status of neonates
with sepsis are difficult to analyze because the usual nutri-
tional indicators such as weight, weight for age, or weight
for length are affected by clinical factors and the appliances
used for an adequate management of intravenous fluids,
oxygen, and ventilation. Therefore, different alternatives
such as changes in body composition should be used. This
article reports changes in body composition of DHA-sup-
plemented and non-supplemented neonates during an epi-
sode of sepsis.
Materials and methods
This study is part of a larger investigation designed to
evaluate potential effects of DHA supplementation on nu-
tritional status, immune and inflammatory responses, and
anorectic reaction to infections in infants. Results regarding
the role of DHA on the anorectic response to infection have
been published elsewhere [10,11]. In this article we are
reporting results related to the probable protective effect of
supplementation on nutritional status.
Patients
A randomized, double-blind, placebo-controlled trial
was conducted at our nutrition research department. The
patients were selected from our neonatal intensive care
department. Term and preterm neonates who developed
sepsis after a surgical procedure, but with functional gas-
trointestinal tract, were eligible. Neonates who required a
blood transfusion and those who were undernourished at
birth according to the criteria of Lubchenco et al. [12] were
excluded. Infants were selected at sepsis diagnosis and ran-
domly assigned to receive a daily dose of 100 mg of DHA
(Neuromins for Kids, Martek Biosciences, Columbia, MD,
USA) or placebo (100 mg olive oil) administered by enteral
route for 14 d. Randomization was conducted by ascribing
codes A and B to treatments; codes were open after statis-
tical analysis. Parents of the neonates signed an informed
consent form after the study protocol and the potential
benefits and risks were explained. The study protocol was
reviewed and approved by our ethics committee.
Clinical and laboratory parameters
At selection, a blood sample was obtained from a pe-
ripheral vein to determine erythrocyte fatty acid composi-
tion. Illness severity was determined at sepsis diagnosis
with the Score for Neonatal Acute Physiology (SNAP-II)
questionnaire using data from medical records. The type and
amount of feeding were recorded daily to determine energy
intake.
Body composition determination
Anthropometric and body composition measurements
were obtained at baseline and d 14 of follow-up. We are
now reporting results of a group of neonates in whom
measurement of body composition by the deuterium dilu-
tion technique was available because they were not vomit-
ing or receiving diuretics.
Body composition was determined by the plateau
method because it only requires one sample after equilib-
rium, with fewer interventions to the patient who is septic
[13]. A dose of 0.12 g of deuterium oxide per kg body
weight (Martek Biosciences) in 1 mL of sterilized water was
administered by orogastric tube. The tube was washed four
times with 0.5 mL of sterilized water. Urine was collected
with cotton swabs placed into disposable diapers or into
urine bags before deuterium administration and at 2-h in-
tervals for 8 h [14]. Deuterium enrichment of the samples
was measured in samples of 1 ␮L of urine after chromium
reduction of water into hydrogen gas at 850°C with an
H-device. Hydrogen gas was analyzed in an isotope-ratio
mass spectrometer (Finningan Delta-plus, Bremen, Ger-
many) coupled online to the H-device. To avoid memory
effect, each sample was measured 6 times using Standard
Mean Ocean Water (SMOW) and Standard Light Antarctic
Precipitation (SLAP) as standards. Only the last two mea-
surements were used for calculations. Total body water was
calculated from the change in the deuterium concentration
from the basal to the postdose sample. Fat-free mass was
calculated using a hydration constant of 0.805 [15]. Body
fat mass (FM) was calculated by subtracting fat-free mass
from total body mass.
Weight was measured using an electronic balance with a
precision of 1 g (Sartorious, Gottingen, Germany); length
 M. López-Alarcón et al. / Nutrition 22 (2006) 731–737
was obtained with an infantometer to the nearest 1 mm
(Seca, Hamburg, Germany), and head circumference was
obtained with a non-stretchable tape with 1-mm precision
(Seca). All measurements were obtained in triplicate.
Erythrocyte fatty acids
Blood samples were centrifuged within 30 min of col-
lection at 2000 ⫻ g for 15 min at 4°C. Plasma was removed
immediately after centrifugation, and the erythrocyte pellet
was washed twice with 0.9% sodium chloride (NaCl) solu-
tion and stored at ⫺20° C until analysis. Total fat was
extracted from 0.5 g of frozen erythrocytes with 4.5 mL of
isopropanol with butylated hydroxytoluene added as an an-
tioxidant (10 ␮g/mL final volume). Tubes were shaken for
15 min and centrifuged at 1200 ⫻ g for 5 min at 4°C; the
clear supernatant was poured off and dried at 60°C under a
nitrogen stream. Fatty acids were methylated with methan-
olic chloridic acid 3 Normal (HCI 3N). Methyl esters were
extracted with hexane and analyzed by gas chromatography
(589 Series II, Hewlett Packard, Avondale, PA, USA) using
a 100-m ⫻ 0.2-mm inside diameter fused silica column
coated with 0.2 ␮m CP Sil 88 (Chrompak, Middleburg, The
Netherlands) and a flame ionization detector. Fatty acids
were identified from chromatograms by comparison with
known standards. Fatty acid concentrations were calculated
by use of response factor of standard fatty acids. Heptade-
canoic acid was added to samples as internal standard.
Results were expressed as weight percentages (%/total
weight) of total fatty acids with carbon chain lengths from
14 to 24 carbon atoms.
Energy intake
The amount of parenteral liquids, formula, and human
milk administered orally to infants was measured and re-
corded daily to determine energy intake. Energy intake from
formula was derived from information reported by the man-
ufacturer. Energy content of human milk was assumed to be
2.73 kJ/mL, which is the average of energy provided by
human milk in developing countries [16].
Illness severity
The SNAP-II questionnaire was used to evaluate illness
severity at baseline. The SNAP-II questionnaire takes into
account six physiologic variables such as blood pressure,
temperature, the PO2/fraction of inspired oxygen ratio, se-
rum pH, seizures, and urine output. The higher the SNAP-II
score, the more severe the disease is [17].
Statistical analysis
Software (Minitab 14, State College, PA, USA) was used
for statistical analysis. Differences were considered signif-
icant at P ⱕ 0.05. Because not all variables were normally
733
distributed, results are expressed as mean ⫾ SD or as
median (minimum, maximum) as appropriate. Energy in-
take was expressed in joules and adjusted by body weight.
Study data were analyzed on an intent-to-treat basis
including all neonates who entered the deuterium body
composition study (n ⫽ 27). For this analysis, neonates
were classified into two groups: those who gained in FM ⫽
1, and those who did not present any gain ⫽ 0; relative risk
(RR) and confidence interval were obtained.
Because the sample presented here was extracted from a
high-risk population of patients, a subgroup analysis was
prospectively planned to analyze results from neonates who
strictly completed the follow-up. Comparisons between
groups were conducted with Mann-Whitney test. Within
comparisons were performed with the sign test. A multiple
regression model was used to analyze the effect of DHA on
nutritional status adjusting by confounders such as energy
intake, erythrocyte DHA, and illness severity.
Results
Patient characteristics
In all, 27 neonates were followed up, 16 received
DHA and 11 received placebo. Five patients died during
the follow-up period: four neonates (one with DHA and
three with placebo) died within the first 5 d after selec-
tion; another neonate (with DHA) died at day 13 of
follow-up. The surgical procedure and the isolated germ
for each infant are presented in Table 1. Baseline char-
acteristics of neonates who completed the follow-up pe-
riod and neonates who died are presented in Table 2.
Although there was no difference in any of the variables,
the SNAP-II score and the leukocyte count tended to be
higher and the platelet count lower in children who died
than in those who completed the follow-up (either DHA
or placebo). The mean proportion of DHA in erythrocytes at
baseline was higher in neonates in the placebo group than
infants in the DHA group (P ⫽ 0.04). There was no difference
in any other fatty acid (Table 3).
Clinical evolution
In all, 87% of placebo neonates and 50% of the DHA
neonates were receiving a certain amount of total parenteral
nutrition at selection, but there was no difference in the
amount of energy that neonates received per day in the first
or in the second week of follow-up. Similarly, the amount of
energy from human milk was not different between groups
(P ⫽ 0.45 and 0.26 in the first and second week, respec-
tively). None of the formulas fed to the infants provided any
amount of eicosapentanoic acid or DHA.
There was no difference in the use of corticosteroids,
antibiotics, or mechanical ventilation, or any of the vari-
ables related with the clinical evolution between groups
734 M. López-Alarcón et al. / Nutrition 22 (2006) 731–737

Table 1 Table 3
Diagnosis and isolated germ of neonates Erythrocyte fatty acid composition of neonates who completed the
follow-up period, stratified by treatment
Patient Treatment Surgical procedure Germ
Treatment
1 DHA Correction of anomalous Staphylococcus sp.
vein connection DHA Placebo P value
2 DHA Systemic-pulmonary shunt Klebsiella pneumoniae
3 DHA Resection of myxoma Enterobacter cloacae Arachidonic acid 9.24 ⫾ 1.89 10.63 ⫾ 1.15 0.06
4 DHA Repair of coarctation NGI Eicosapentanoic acid 0.36 ⫾ 0.20 0.49 ⫾ 0.39 0.53
5 DHA Colostomy NGI Docosahexaenoic acid 2.49 ⫾ 0.73 3.06 ⫾ 0.44 0.04
6 DHA Repair of esophagus NGI AA/DHA 3.89 ⫾ 0.87 3.55 ⫾ 0.66 0.33
7 DHA Tracheotomy Klebsiella sp. DHA, docosahexaenoic acid; AA/DHA, arachidonic acid/docosahexae-
8 DHA Ventriculoperitoneal shunt Staphylococcus aureus noic acid.
9 DHA Closure of ductus arteriosus Coagulase-negative % Totalweight.
staphylococci
10 DHA Placation of diaphragm Serratia marcescens
11 DHA Repair of esophagus Coagulase-negative
staphylococci Assessment of changes in nutritional status
12 DHA Closure of ductus arteriosus NGI
13 DHA Closure of ductus arteriosus NGI Anthropometric and body composition measurements at
14 DHA Correction of tetralogy of Staphylococcus aureus
Fallot
baseline and at the end of follow-up were comparable be-
15† DHA Posterior sagittal Streptococcus faecalis tween groups (Table 5). However, DHA neonates presented
anorectoplasty a significant increase in total body mass and FM, whereas
16† DHA Ileostomy Staphylococcus aureus placebo neonates did not present any increase (Fig. 1).
17 Placebo Repair of diaphragmatic NGI Comparisons between groups demonstrated that changes in
hernia
18 Placebo Fundoplication NGI
FM were significantly greater in the DHA group (P ⫽ 0.03).
19 Placebo Ventriculoperitoneal shunt Serratia marcescens Although length and head circumference increased in both
20 Placebo Repair of coarctation Serratia marcescens groups (P ⬍ 0.01), length gain tended to be greater in
21 Placebo Fundoplication Coagulase-negative infants who received DHA than in the placebo group (25
staphylococci versus 10 mm, P ⫽ 0.07). There was no difference in head
22 Placebo Fundoplication NGI
23 Placebo Repair of aortic arch NGI
circumference between groups (20 versus 25 mm, P ⫽
24 Placebo Colostomy NGI 0.37).
25† Placebo Repair of diaphragmatic Coagulase-negative A regression analysis including supplementation as a
hernia staphylococci covariate indicated that compared with placebo group, FM
26† Placebo Systemic-pulmonary shunt Klebsiella sp. increased only in DHA neonates after adjusting by erythro-
27† Placebo Systemic-pulmonary shunt NGI
and atrioseptostomy
cyte DHA, illness severity, energy intake, gestational age,
and sex (Table 6).
NGI, no germ isolated; DHA, docosahexaenoic acid. Relative risk (RR) analysis suggested a protective effect
†
Died.
of DHA supplementation, although no statistical signifi-
cance was reached (RR ⫽ 0.43, confidence interval ⫽
(Table 4). The number of patients with hemorrhages or 0.13–1.45, P ⫽ 0.18). In the intent-to-treat analysis, i.e.,
clotting alterations such as prothrombin time and partial including infants who died as if they did not gain FM, the
thromboplastin time were also not different, suggesting no protective effect remained (RR ⫽ 0.49, confidence interval
side effects of DHA. ⫽ 0.21–1.15, P ⫽ 0.10).

Table 2
Baseline clinical and nutritional characteristics of neonates with sepsis
DHA (n ⫽ 14) Placebo (n ⫽ 8) Died (n ⫽ 5)

Gestational age (wk) 37.7 ⫾ 2.7 37.8 ⫾ 1.2 37.6 ⫾ 5.3

Postnatal age (d) 26.1 ⫾ 3 28.2 ⫾ 5 21.6 ⫾ 23.4
Weight (g) 2771 ⫾ 728 2797 ⫾ 562 2662 ⫾ 978
Length (cm) 49.2 ⫾ 4.6 48.5 ⫾ 4.1 47.0 ⫾ 4.9
Head circumference (cm) 33.0 ⫾ 2.0 33.1 ⫾ 1.7 31.5 ⫾ 3.3
SNAP-II 14.9 ⫾ 12.7 13.3 ⫾ 11.9 19.2 ⫾ 4.4
Leukocytes (cells/mm3) 14 003 ⫾ 6490 13 870 ⫾ 9083 19 948 ⫾ 20 954
Platelets (cells/mm3) 201 321 ⫾ 107 156 234 888 ⫾ 113 926 117 040 ⫾ 91 505
Energy, kJ/kg/d 294.71 ⫾ 78.52 349.07 ⫾ 131.0 333.54 ⫾ 102.66

DHA, docosahexaenoic acid; SNAP, Score for Neonatal Acute Physiology.

Values expressed as mean ⫾ SD.
 M. López-Alarcón et al. / Nutrition 22 (2006) 731–737 735

Table 4
Clinical and feeding characteristics throughout the follow-up
DHA (n ⫽ 14) Placebo (n ⫽ 8) Died (n ⫽ 5)

Vasopressors/inotropics
Yes* 5 (35.7) 3 (37.5) 0
Duration (ds) 13 (1–14) 11.5 (1–14) 0
Antibiotics
Yes* 14 (100) 8 (100) 5 (100)
Duration (ds) 11 (7–14) 14 (5–14) 3 (1–13)
Corticosteroids, Yes* 6 (42.9) 2 (25) 2 (40)
Duration (ds) 1.5 (1–4) 3 (2–4) 1
Ventilation
Yes* 11 (78.6) 6 (75) 4 (80)
Duration (ds) 14 (7–14) 14 (14) 2.5 (1–5)
Leukocytes† (cells/mm3)
Baseline 11.45 (5.91–27.20) 15.40 (2.08–24.60) 12.90 (3.14–56.30)
Final 9.69 (7.95–18.40) 11.25 (7.82–19.50) 10.41 (3.62–17.20)
Platelets† (cells/mm3)
Baseline 166.00 (60.60–364.00) 208.50 (98.10–439.00) 136.00 (6.50–205.00)
Final 216.50 (87.10–333.00) 262.00 (185.00–481.00) 54.50 (35.00–74.00)
C-reactive protein‡
Baseline 15.9 (4.8–126.5) 97.0 (1.9–158.3) 38.92 (7.11–106.3)
Final 10.2 (0.23–84.8) 11.9 (1.6–49.2) ND
Nutrition pathway*
Enteral 7 (50) 1 (12.5) 1 (20)
TPN 0 0 2 (40)
Enteral ⫹ TPN 7 (50) 7 (87.5) 2 (40)
Energy intake§
First week 330.87 (149.24–542.43) 363.26 (282.08–483.81) 309.55 (191.88–442.80)
Second week 384.58 (99.63–644.11) 391.55 (282.90–507.17) 285.77
Energy from milk§
First week 21.73 (0–239.85) 14.76 (0–76.67) 72.49
Second week 35.26 (0–441.16) 19.68 (0–127.92) 103.48

ND, not determined; DHA, docosahexaenoic acid; TPN, total parenteral nutrition.
Median (minimum-maximum).
* Count (percentage);
†
thousand;
‡
mg/L;
§
kJ/kg/d.

Discussion Studies in human beings have found that using long-term

This study presents evidence that supplementation with
DHA may protect the nutritional status of neonates with
sepsis. Such protection was achieved by providing the fatty
acid in the acute phase of infection, i.e., when the infection
was already established. A study designed to demonstrate
such positive effect of DHA supplementation is warranted.
dietary supplementation with ␻-3 fatty acids suppresses
cytokine production by mononuclear leukocytes [18] or
improves the course of inflammatory diseases [19,20]. Ac-
cording to these studies, weeks to months are needed for the
full effect of ␻-3 fatty acids to become effective. In addi-
tion, some studies in human beings have reported beneficial
effects of acute supplementation with ␻-3 fatty acid when

Table 5
Body composition at baseline and at d 14 of follow-up in septic neonates, stratified by treatment
Baseline Day 14

DHA Placebo DHA Placebo

TBM (g) 2995 (1698, 4120) 2821 (1810, 3690) 3063 (1810, 3841) 2776 (1786, 3520)
TBW (g) 1845 (1210, 2720) 1985 (1170, 2250) 1920 (1290, 2450) 1910 (1090, 2250)
FFM (g) 2315 (1520, 3420) 2495 (1470, 2830) 2415 (1620, 3080) 2395 (1380, 2830)
FM (g) 390 (110, 730) 370 (130, 1050) 465 (160, 980) 385 (150, 970)
FM (%) 12.93 (5.18, 25.30) 13.37 (5.69, 28.5) 14.11 (7.5, 25.59) 12.89 (5.93, 27.38)

TBM, total body mass; TBW, total body water; FFM, fat-free mass; FM, fat mass; DHA, docosahexaenoic acid.
Median (minimum-maximum)
736 M. López-Alarcón et al. / Nutrition 22 (2006) 731–737

low leukocyte counts in the DHA group gained FM, sup-

porting the knowledge that ␻-3 fatty acids are not just
antiinflammatory agents but instead provide a wide range of
benefits that result in a better-modulated immune response.
In our study, although the proportion of DHA in the
membrane of erythrocytes was borderline associated with
FM gain, it is important to recognize that placebo neonates
who did not show an increase in FM presented higher
proportions of this fatty acid at baseline. This finding sup-
ports an independent effect of supplementation likely be-
cause DHA administered in the acute phase of infection is
rapidly available for leukocytes for a better-modulated in-
flammatory response with lower metabolic side effects.
Studies exploring this mechanism by comparing cytokine
Fig. 1. Within differences in body composition measurements (base-
line– day 14) are presented. Placebo neonates (slashed bars) did not
production in DHA-supplemented and non-supplemented
show increase in body composition; in contrast, docosahexaenoic acid septic neonates, and DHA incorporation to leukocytes, are
(DHA) neonates (gray bars) showed significant increase in total body underway.
mass and fat mass (P ⬍ 0.05). Between group differences were signif- Thus, results from this group suggest that administra-
icant only for fat mass (P ⫽ 0.03).
tion of DHA protects nutrition deterioration of septic
neonates, at least in those who do not present a severe or
these are administered by parenteral nutrition. The benefits complicated septic episode. The authors recognize, how-
are reported on modulation of cytokine response [21,22] and ever, that such results must be interpreted with caution
in a better clinical outcome of surgical patients such as and confirmed in the entire sample, i.e., including in the
decreased mortality, less use of mechanical ventilation, less analysis all neonates who are followed up (measured with
use of antibiotics, and shorter hospital stay [23,24]. How- deuterium or with anthropometry). Nevertheless, some
ever, benefits of parenteral supplementation are expected strength should be recognized. Measurements of body
because the fatty acid does not need to be absorbed and composition with the deuterium dilution technique pro-
transported to blood flux. On the other hand, ␻-3 fatty acids vided high-quality data obtained using a precise method,
administered intravenously may also produce adverse ef- contrary to anthropometry, which was used for the anal-
fects because this leads to a massive increase in plasma free ysis of body composition in the entire sample. However,
fatty acids, which are already increased in septic individu- even with this small sample size, significant differences
als. With this study we are presenting evidence that admin- were detected.
istration of DHA to infants with sepsis may provide a In conclusion, it appears that acute DHA supplementa-
benefit when administered by orogastric pathway in the tion helps to protect nutritional status of septic neonates.
acute phase of infection. However, these results should be confirmed in a sample of
The mechanisms of such a probable protective effect
children with more severe episodes.
were not explored. It is possible that the direct consequence
of DHA supplementation is to decrease the production of
cytokines decreasing secondarily their catabolic effect [6].
Another mechanism is the production of eicosanoids with Table 6
lower biological potency than those derived from ␻-6 fatty Variables associated with changes in fat mass in a group of septic
acids, which may result in an attenuated inflammatory re- neonates
sponse [5,6]. Alternatively, DHA supplementation may pro- Coefficient SE P value r2
tect nutritional status of neonates by the production of lipid
Intercept ⫺221.80 146.2 0.15
mediators generated from DHA that seem to more quickly Sex*, male 51.54 31.85 0.13
limit the inflammatory response by shortening neutrophil Term† ⫺23.82 36.00 0.52
infiltration [25]. Energy intake (kcal/kg/d) 0.003 0.18 0.98
Interestingly, DHA supplementation demonstrated a pos- Illness severity, SNAP-II ⫺0.66 1.44 0.66
Erythrocyte DHA (%) 47.48 24.92 0.07
itive effect on nutritional status even in those neonates with
DHA group‡ 117.65 39.23 0.01
low leukocyte counts. This is important when considering 0.08 0.53
the treatment of patients with sepsis because administration
DHA, docosahexaenoic acid; SE, standard error; SNAP, Score for Neo-
of antiinflammatory agents may harm some patients with
natal Acute Physiology.
immunoparalytic characteristics. In this study, DHA was * Compared with female,
administered to all patients including those with leukocyte †
compared with preterm,
counts ⬍10,000 cells/mm3 and two of the three infants with ‡
compared with placebo group.
 M. López-Alarcón et al. / Nutrition 22 (2006) 731–737
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