Open Journal of Pediatrics, 2012, 2, 214-218 OJPed
http://dx.doi.org/10.4236/ojped.2012.23034 Published Online September 2012 (http://www.SciRP.org/journal/ojped/)
Continuous versus bolus nasogastric tube feeding in
premature neonates: Randomized controlled trial*
M. van der Star1,2, Ben Semmekrot1#, Esmeralda Spanjaards1, An n e Scha a fs ma3
1Department of Pediatrics, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands
2University Medical Center St. Radboud, Nijmegen, The Netherlands
3FrieslandCampina, Innovation Infant & Toddler Nutrition, Leeuwarden, The Netherlands
Received 13 March 2012; revised 11 April 2012; accepted 28 May 2012
ABSTRACT
Background: Whether premature infants should be
fed by bolus or continuous gavage feeding, is still a
matter of debate. A recent Cochrane analysis re-
vealed no difference. Study design and methods: We
carried out a randomized controlled trial in prema-
ture infants on continuous versus bolus nasogastric
tube feeding, to search for differences with respect to
number of incidents, growth, and time to reach full
oral feeding. In total, 110 premature neonates (gesta-
tional age 27 - 34 weeks) were randomly assigned to
receive either continuous or bolus nasogastric tube
feeding. Basic characteristics were comparable in
both groups. Results: No significant difference in
weight gain could be detected between the two groups,
mean weight gain amounting 151.6 (108.9 - 194.3) and
152.4 (102.2 - 202.6) grams per week in the continu-
ous and bolus group, respectively. No significant dif-
ferences were found between both groups in the time
needed to achieve full oral feeding (8 oral feedings per
day), full oral feeding being achieved at day 31 (range
19 - 43) and day 29 (range 18 - 40) of life in the con-
tinuous and bolus group, respectively. We also found
no significant differences in the number of “inci-
dent-days” (three or more incidents a day): 3.5 (0 - 9)
versus 2.7 (0 - 6.5) days in the continuous and bolus
group, respectively. Conclusion: No significant dif-
ferences were found in weight gain, time to achieve
full oral feeding and number of incident-days be-
tween preterm infants enterally fed by nasogastric
tube, according to either the bolus or continuous me-
thod.
Keywords: Premature; Infant; Tube Feeding; Bolus
Feeding; Continuous Feeding
1. INTRODUCTION
Most premature infants must initially be fed by gastric
tube because of their inability to either suck effectively
or coordinate sucking, swallowing and breathing.
Several approaches exist as to tube feeding of preterm
infants. An important difference in approach is whether
to feed them continuously o r by intermittent bolus.
Advantages of bolus feeding mentioned in the literature
are the natural character of this type of feeding. Cyclical
surges of various gastrointestinal tract hormones occur
after feeding preterm infants by bolus [1-3].
On the other hand, continuous feeding would be less
exhausting and lead to less incidents than intermittent
feeding [4,5]. Also, functional limitations of the premature
infant’s gastrointestinal system such as delayed gastric
emptying or intestinal transit could hinder its ability to
handle bolus milk feeds, resulting in feeding intolerance
[6-11].
Studies investigating the superiority of either type of
feeding (bolus or continuous) are characterized by small
numbers, poor definitions of patient groups and poor
definitions of parameters to evaluate the differences,
such as time to full oral feeds and number of incidents.
While we were writing this manuscript, a Cochrane
analysis of studies investigating bolus versus continuous
feeding occurred, revealing that time to achieve full oral
feeds did not differ between the two methods used in
infants of less than 1500 grams [12]. No significant
differences in somatic growth and incidence of necrotizing
enterocolitis (NEC) occurred between feeding methods
irrespective of gastric tube placement. However, small
sample sizes, methodologic limitations, inconsistencies
in controlling variables and conflicting results make it
difficult to make universal recommendations regarding
the best tube feeding method for premature infants.
We present a large randomized study with sufficient
power on bolus versus continuous enteral feeding in
premature infants with a nasogastric tube in order to
detect any difference in clinical effects between the two
*In patients that could not be fed human milk, premature formula was
kindly provided by FrieslandCampina. Authors MvdS, BS and ES have
no financial relationships w it h F rieslandCampina.
#Corresponding author.

M. van der Star et al. / Open Journal of Pediatrics 2 (2012) 214-218 215
types of feeding.
2. METHODS
2.1. Study Design
This non-blinded rando mized study wa s performed at the
neonatal unit of the Canisius-Wilhelmina Hospital, a
level 2 hospital, in Nijmegen, the Netherlands. Infants
were enrolled within the first days of life, directly after
birth or after discharge from the neonatal intensive care
unit of the adjacent level 3 university hospital. They were
assigned randomly to continuous nasogastric feeding
(CNF) or intermittent bolus nasogastric feeding (IBNF).
The randomization assignment was performed using
sealed envelopes.
In a preceding pilot study in 19 patients with continuous
feeding, we observed a mean number of incidents of 2.1
(SD 1.7). Assuming that the standard deviation in the
bolus group would also be 1.7, and based on an un-
reliability of 5% and a power of 80%, it was calculated
that 51 patients would be needed in either group, to show
a mean difference of maximal one incident per day.
Informed written consent was obtained from both parents
and the study protocol was approved by the local research
ethics committee. The study was performed according to
GCP-guidelines.
2.2. Study Population
A total of 110 premature infants were enrolled between
November 2001 and September 2004. They were recruited
into the study if they satisfied all the following criteria:
gestational age 27 - 34 weeks; need of nasogastric tube
feeding; clinically stable condition to start feeding soon
after birth (until the third day); informed consent from
both parents. Infants were excluded if they had a severe
congenital malformation, used prokinetics, or had evidence
of infection (clinical signs and symptoms of infection
and elevated C-reactive protein).
Infants were followed until they tolerated full oral
feeds and had no longer need of their nasogastric tube
(which for this reason was removed).
2.3. Feeding Protocol
After entry into the study, all patients received a
nasogastric tube. Continuous feeds were delivered by an
infusion pump over 1 - 2.5 hours, an infusion time of 1
hour being used only in case of 24 feedings a day. Bolus
feedings were given over 10 - 20 minutes by gravity
drainage every two or three hours.
On day one, feeds were started at 60 mL/kg/day, with
a daily increment of 20 mL/kg. Full fluid and energy
requirements were met at 160 - 180 mL/kg/day. This
feeding protocol was similarly used in both groups.
Expressed human milk, when available, was the
nutrition of choice. When human milk was not available,
preterm formula (335 kJ/80 kcal per 100 mL, Frisopré,
FrieslandCampina, The Netherlands) was used.
According to the local feeding protocol, breastmilk
fortifier (1.75 g (6 kCal) per 50 ml breast milk, Friso
BMF, FrieslandCampina) is added in infants of both
groups, as soon as fluid intake reaches 50 mL/kg/dag.
Non nutritive sucking is introduced as soon as gestational
age reaches 32 weeks and/or body weight reaches 1500 g.
In infants on bottle feeding, a bottle is presented as soon
as gestational age reaches 34 weeks and/or body weight
reaches 1500 g.
2.4. Outcome Measures
A “trial-list” was developed for each infant to be kept on
the bedside, on which the nurses noted any incident
occurring. The following incidents were recorded: fre-
quency of apnea, bradycardia and desaturations.
An apnea was defined as a cessation of inspiratory gas
flow for a duration of 20 seconds (on cardiorespiratory
monitor). The nurses noted the frequency of apneas
during their shift, including the time period during which
breathing stopped, until th e infan t’s complete recove ry of
respiration and oxyg en saturation.
Bradycardia was defined as a decline in heart rate at
less than 80 beats per minute. The nurses also noted the
frequency, the period of time, the lowest heart rate
reached and the recovery.
To simplify scoring, three or more incidents a day was
scored as one “incident-day”.
All infants were weighed each morning, naked, before
feeding and bathing, on one same electronic weighing
scale with a one-gram accuracy. Growth was assessed
from birth to the day of tolerating full feeds. Weekly
weight increments were noted.
Feeding tolerance was assessed by recording the
number of days the infant needed to tolerate full milk
feeds (8 oral feedings per day) and by the number of
“incident-days” (days with more than 3 incidents).
2.5. Data Analyses
Data were analyzed with the SPSS 15.0. An independent
T-test and the Mann -Whitney test were used for assessing
differences between groups (CNF and IBNF) since the
Kolmogorov-Smirnov test assumed parameters to be
normally distributed.
3. RESULTS
Of all eligible infants born between November 2001 and
September 2004, 110 were randomly assigned to the
feeding groups. Seven infants (6.4%) were excluded after
randomization because of serious gastro-esophageal reflux

M. van der Star et al. / Open Journal of Pediatrics 2 (2012) 214-218 216
(0.9%), incarcerated hernia (0.9%), suspected necrotizing
enterocolitis (1.8%), feeding problems needing tube
feeding at home until the age of 2 years (0.9%), and
unacceptable growth needing extra supplements (0.9%).
One patient was missed (0.9%). The two infants with
suspected necrotizing enterocolitis were given bolus
feeding; the diagnosis could not be confirmed, infants
were treated conservatively and had no further intestinal
problems (both Bell’s stage 1).
There was only one refusal for the study, This
concerned an infant whose parents insisted to have their
infant on continuous feeding, since they felt it would be
better tolerated.
There were no statistically significant differences
between infants in both groups in baseline demographic
and clinical characteristics at study entry (Table 1 ). Also,
no significant differences were present between groups
for the number of infants who were removed from the
study.
There was no significant difference in weight gain
between the two groups. The mean weekly increment
was 151.6 grams (rang e 108.9 - 194.3) in th e continuous
group, versus 152.4 (range 102.2 - 202.6) in the bolus
group.
We found no significant differences between groups in
the time taken to achieve full feeds (8 oral feedings per
day). Full oral feeding (means and range) was achieved
at 31 (19 - 43) days of life in the continuous group,
versus 29 (18 - 40) days in the bolus group.
Table 1. Basic demographic and clinical characteristics of pa-
tients at study entry.
Continuous (n = 51) Bolus (n = 52)
Gestational age (wk) and (SD) 32.3 (1.2) 32.3 (1.1)
Males, n (%) 23 (45) 26 (50)
Birth weight (g) and (SD) 1670 (352) 1735 (347)
Type of feeding
Human milk, n (%) 34 (67) 37 (71)
Formula, n (%) 17 (33) 15 (29)
IRDS, n (%) 15 (29) 13 (25)
Intracranial hemorrhage, n (%) 1 (2) 3 (6)
Coffeine 33 (65) 28 (54)
Need of oxygen 10 (20) 13 (25)
Excluded (%) 3 (5.9) 4 (7.7)
Also, no significant differences in the number of “in-
cident-days” were found. The continuous group showed
a mean of 3.5 (range 0 - 9 ) “incident-days”. The bolus
group showed a mean of 2.7 (range 0 - 6.5) days (Table
2). Calculated as total number of incidents, there were
also no differences in the number of incidents between
the two study groups (data not shown) .
None of the infants in either group developed necro-
tizing enterocolitis.
4. DISCUSSION
We conducted a randomized controlled trial in preterm
infants to study the clinical effects of continuous versus
bolus nasogastric tube feeding.
No significant changes between the two types of feed-
ing were found on the number of incident-days, time
needed to reach full oral feeding, weight gain and total
time of admission.
Our study has a number of strengths. We carefully
calculated the power needed to find a significant differ-
ence in the number of incidents. Preceding the study, we
clearly defined the clinical parameters to use in measur-
ing the effects. Also, we used an intention to treat analy-
sis for evaluation of possible differences.
Drawbacks of the study are the absence of blinding for
the patients, doctors, nurses, and other caregivers in-
volved, and absence of a placebo-control group. It was
felt that blinding would be too difficult to perform for
practical reason, as would be the use of placebo feeding.
An extra team of caregivers would have been needed,
which, for practical and financial reasons, was not feasi-
ble.
However, we feel that the results are robust, since only
few patients failed randomization and results are those of
intention to treat analyses.
Several studies in the past have given different results.
Schanler et al. found no differences between groups in
the number of days on which feedings were interrupted
for feeding intolerance, as assessed by gastric residual
volume [13] . We di d not measure gastric resi dual volume
in our study, since it was not seen as a useful parameter.
Apart from the exclusions indicated, no feeding
interruptions for intolerance occurred. Toce et al. found
no difference between groups in the average number of
hours spent nil per os per day for feeding intolerance [14].
Similarly, Akintorin found no difference in the number
Table 2. Results.
Continuous (n = 51) Bolus (n = 52)
“Incident-days” 3.5 (0 - 9) 2.7 (0 - 6.5)
Postnatal age at reaching full oral feedings (days) 31 (19 - 43) 29 (18 - 40)
Mean weekly increment of weight (grams) 151.6 (108.9 - 194.3) 152.4 (102.2 - 202.6)
Data presented as means (range).

M. van der Star et al. / Open Journal of Pediatrics 2 (2012) 214-218 217
of infants who experienced feeding intolerance, defined
as feeds held longer than 12 hours [15]. More recently,
Dsilna et al. found no difference in feeding intolerance
defined as the number of occasions the infant was
diagnosed with suspected necrotizing enterocolitis (Bell
Stage I) followed by interruption of enteral feeds for at
least 8 hours [8]. A meta-analysis could not be performed
because modes of measuring feeding intolerance were
not comparable. Schanler reported that infants fed by the
continuous feeding method gained weight slower than
infants fed by the intermittent bolus feeding method [13].
Toce, however, did not find a difference in weight gain
(grams per kg per day) between the two groups [14].
Similarly, Macdonald et al. and also Silvestre et al. both
found no difference in weight gain (grams per week)
between the two groups [11,16].
The most recent Cochrane analysis reported that
overall, the seven included trials, involving 511 infants
of less than 1500 grams, found no differences between
the two feeding methods in time to achieve full enteral
feeds [12].
In the subgroup analysis of those studies comparing
continuous versus intermittent bolus nasogastric milk
feedings, the findings remained unchanged. There was
no significant difference in somatic growth and incidence
of NEC between the two feeding methods. One study
noted a trend toward more apneas during the study
period in infants fed by the continuous tube feeding
method compared to those fed by intermittent feedings
delivered predominantly by orogastric tube placements.
In subgroup analysis based on weight groups, one study
suggested that infants less than 1000 grams, and 1000 -
1250 grams birth weight, gained weight faster when fed
by the continuous nasogastric tube feeding method com-
pared to intermittent nasogastric tube feeding. A trend
was observed toward earlier discharge for infants less
than 1000 grams birth weight fed by the continuous tube
feeding method compared to intermittent nasogastric tube
feeding.
In conclusion, in line with other studies, we found no
differences in either weight gain, time to achieve full oral
feedings, or number of incidents between premature
babies fed by either continuous or bolus nasogastric tube
feeding methods.
5. ACKNOWLEDGEMENTS
The authors greatly acknowledg e th e ea rlier con tributions of doctors M.
Molenschot, I. Zonnenberg and M. de Vries, residents at the time, to
the preparation and performance of this study.
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