Effect of early introduction of minimal enteral feeding on growth and rate of achieving optimal nutritive intake in very low birth weight preterm infants

Abstract

Introduction/Objective Minimal enteral nutrition (MEN) has an important stimulative effect on morphological and functional development of gastrointestinal system in preterm infants. The aim of this study was to assess effects of early introduced MEN on rate of achieving optimal enteral nutritive intake and on body weight, body length, and head circumference gain in very low birth weight (VLBW) premature infants. Methods This prospective study included 45 VLBW newborns (1,010-1,450; 1,350 ± 305 g), in 30 newborns MEN was introduced within three days after birth, and in 15 newborns enteral intake was introduced after five days due to hemodynamic and metabolic instability. Assessment of effect of early MEN

Full text

336
Received • Примљено:
Februry 5, 2016
Accepted • Прихваћено:
March 7, 2016
Online rst: February 21, 2017
DOI: https://doi.org/10.2298/SARH160205024M
UDC: 613.2.032.33-053.32
Correspondence to:
Vesna MARINKOVIĆ
Institute for Neonatology
50 Kralja Milutina St.,
11000 Belgrade
Serbia
vesnam55@ptt.rs
ORIGINAL ARTICLE / ОРИГИНАЛНИ РАД
Effect of early introduction of minimal enteral
feeding on growth and rate of achieving optimal
nutritive intake in very low birth weight preterm
infants
Vesna Marinković1, Niveska Božinović-Prekajski1, Milica Ranković-Janevski1, Zorica Jelić1,
Vesna Hajdarpašić1, Nedeljko Radlović2,3,4
1Institute for Neonatology, Belgrade, Serbia;
2University Children’s Hospital, Belgrade, Serbia;
3University of Belgrade, School of Medicine, Belgrade, Serbia;
4Academy of Medical Sciences of the Serbian Medical Society, Belgrade, Serbia
SUMMARY
Introduction/Objective Minimal enteral nutrition (MEN) has an important stimulative effect on mor-
phological and functional development of gastrointestinal system in preterm infants.
The aim of this study was to assess effects of early introduced MEN on rate of achieving optimal enteral
nutritive intake and on body weight, body length, and head circumference gain in very low birth weight
(VLBW) premature infants.
Methods This prospective study included 45 VLBW newborns (1,010–1,450; 1,350 ± 305 g), in 30 newborns
MEN was introduced within three days after birth, and in 15 newborns enteral intake was introduced after
five days due to hemodynamic and metabolic instability. Assessment of effect of early MEN introduction
on the rate of achieving optimal nutritive intake and gain in basic anthropometric parameters was based
on comparison with a group of subjects who had a delayed MEN introduction.
Results Subjects in which MEN was introduced early on had better weight gain (p < 0.05), reached
birth weight sooner (p < 0.05), and achieved optimal enteral intake much sooner (p < 0.05), compared
to subjects with delayed MEN introduction. The difference in body length gain and head circumference
gain was not significant.
Conclusion Early introduction of MEN has a significant positive effect on rate of body weight gain and
on earlier achievement of optimal enteral intake in VLBW preterm infants.
Keywords: very low body weight infants; early minimal enteral nutrition; optimal nutritive intake
INTRODUCTION
With perinatal care improvements in the last
few decades, incidence of neonatal morbidity
and mortality has been significantly decreased.
Very important role goes to adequate nutrition
of these very vulnerable children, and its posi-
tive effects reflect not only on survival rate and
optimal growth and development, but on adult-
hood as well [1].
The development of gastrointestinal system
starts early in the intrauterine period and con-
tinues postnatally. Although highly immature,
morphologically and functionally, gastrointesti-
nal system partially meets, initially very poorly,
basic nutritive needs of premature infant. In a
very complex process of progressive postnatal
functional maturation of the gastrointestinal
system, early introduction of enteral feeding
has a key role as a physiological stimulus [1, 2].
During the 1980s, new tendencies arose ad-
vocating early initiation of enteral nutrition,
which led to the abandonment of long-standing
practice of delayed enteral feeding of premature
infants in intensive care units [1, 2]. Minimal
enteral nutrition (MEN) implies early intake of
primarily mother’s milk in small amounts (up
to 25 mL/kg/day) in premature infants [2]. This
kind of nutrition doesn’t primarily provide op-
timal nutritive balance in premature infants. Its
basic role is contained in trophic influence on
the immature gastrointestinal system, i.e. on the
development of process of food digestion and
absorption, coordination of motility, gastroin-
testinal hormone activity, and on preservation
of intestinal barrier integrity. In that manner
better feeding tolerance is achieved, as well as
faster postnatal growth and development, lower
incidence of sepsis and necrotizing enterocoli-
tis, and shorter hospitalization [2]. Nowadays,
this way of nutrition is generally accepted in
most neonatal intensive care units as an integral
part of treatment of premature infants [3].
The effects of early introduction of MEN
are assessed in regard to body weight (BW),
body length, head circumference, and rate of
achievement of optimal nutritive intake in very
low birthweight premature infants.

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METHODS
This prospective study included 45 very low birth weight
(VLBW) premature infants hospitalized at the Institute
for Neonatology, Belgrade, Serbia, since June 2012 un-
til September 2013. The subjects were divided into two
groups according to the time of MEN introduction: group
A, n = 30, in which after establishing hemodynamic stabil-
ity, normal blood pressure, blood pH above 7.3 and FiO
2
under 40%, MEN was introduced within three days after
birth; and group B, n = 15, in which MEN was introduced
5–10 days (average 6.07) after birth due to hemodynamic
and metabolic instability and/or meteorism (t = 0.02,
p < 0.05). Basic characteristics of both groups of subjects
are presented in Table 1. Distribution of subjects according
to sex was identical between groups. Group A had 14 male
subjects (46.7%) and 16 female subjects (53.3%), and group
B had seven male (46.7%) and eight (53.3%) female subjects.
The basic way of meeting nutritive needs in both group
of subjects during the first days of life was via parenteral
nutrition, while enteral feeding via nasogastric tube was
introduced according to the above mentioned criteria.
Enteral nutrition in all newborns was started with hu-
man milk, be it donor milk or mother’s milk. Daily intake
volume in the first five days was 25 mL/kg/day, and was
increased gradually according to feeding tolerance. When
enteral volume intake of 80 mL/kg/day was achieved, for-
tified human milk was introduced (FM 85 Nestlè, Vevey,
Switzerland) in a dose of 5 g / 100 mL, and/or specialized
milk formula for premature infants (Mil PRE, Impamil
d.o.o., Belgrade, Serbia).
The following parameters were followed in all subjects:
daily gain in body weight, day of achieving birth weight,
weekly increase in body length and head circumference,
and day of achieving optimal enteral intake.
All data obtained during research was analyzed with
SPSS 10.0 for Windows software package. Both parametric
and non-parametric statistical tests were used to analyze
the data. Comparison of the two groups was done using
Student’s t-test and Mann–Whitney U-test, depending on
the data homogeneity. Comparison of data between more
than two groups was done with Kruskal–Wallis test. Sta-
tistical significance was set at p < 0.05.
RESULTS
Subjects with early introduced MEN (group A) compared
to subjects with delayed introduction of MEN (group B)
had a significantly better body weight gain (10.88 ± 3.25 g
vs. 7.73 ± 1.85 g daily; t = 0.017, p < 0.05), and achieved
birth weight sooner (16.38 ± 3.36 days vs. 21 ± 7.16 days;
t = 0.017, p < 0.05) (Figure 1). Also, group A subjects
achieved optimal enteral intake significantly sooner com-
pared to group B (25.7 ± 7.2 days vs. 28.33 ± 7.35 days;
t = 0.021, p < 0.05) (Figure 2).
The difference in weekly gain in body length during the
observed period between subjects in group A (0.45–0.58;
0.51 ± 0.35 cm) and group B (0.45–0.53; 0.49 ± 0.33 cm)
was not significant (t = 0.025, p > 0.05).
The difference in weekly head circumference gain be-
tween group A (0.46–0.67; 0.49 ± 0.21 cm) and group B
(0.44–0.53; 0.5 ± 0.21 cm) during the observed period was
also not significant (t = 0.022, p > 0.05).
DISCUSSION
Because of its stimulating effect on morphological and
functional development of the gastrointestinal system,
Table 1. Basic characteristics of subjects at birth (n = 45)
Characteristics Group A (n = 30) Group B (n = 15)
Range (x
– ± SD) Range (x
– ± SD)
Birth weight (g) 1,000–1,500 1,274.0 ± 144.6 1,000–1,500 1,250 ± 152.2
Gestational age (weeks) 26–32.5 29.5 ± 1.6 27–31.5 29.0 ± 1.2
Apgar score 1’ 1–8 4.9 ± 1.9 2–8 5.53 ± 1.9
Apgar score 5’ 2–8 5.9 ± 1.5 4–8 6.33 ± 1.5
Figure 1. Achievement of birth weight (day)
A:B; p < 0.05
Figure 2. Achievement of optimal nutrition intake (day)
A:B; p < 0.05
Eect of early introduction of minimal enteral feeding in very low birth weight preterm infants

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MEN introduced during the first 24–72 hours after birth
is also known in literature as „trophic feeding“ [4]. Some
authors consider early introduction of MEN to be within
four days after birth [5].
In our subjects, MEN was introduced within the first 72
hours as advocated by most authors [4]. Amount of enteral
intake was also a problem in everyday work, because it
varied greatly between studies. Therefore, MEN was de-
fined as small volume enteral intake, up to 25 mL/kg/day,
or less than 20 kcal/kg/day [6]. MEN was introduced in
our subjects in accordance with the aforementioned rec-
ommendation.
Precondition for the initiation of MEN is clinical state
of a patient, his/her metabolic and hemodynamic stabil-
ity. Precaution should be taken in case of severe perinatal
asphyxia, sepsis, severe hemodynamic instability, absence
of end-diastolic flow, indomethacin therapy and hemody-
namically significant persistent ductus arteriosus, because
of possible necrotizing enterocolitis development [7]. Be-
fore enteral feeding was introduced in our subjects, their
mean arterial pressure was within reference range for body
weight and gestational age, there was no meteorism, and
pH value exceeded 7.3.
It is fully understood nowadays that MEN should be
initiated with mother’s milk, using colostrum whenever
possible [3]. Otherwise, when mother’s milk is not avail-
able, human donor milk from a milk bank is an optimal
choice [8]. Current tendencies show the need for establish-
ing human milk banks which should be the foundation of
nutritive support of premature infants and can contribute
greatly to lactation preservation [9]. It is general attitude
that mother’s milk, with appropriate supplementation,
represents the foundation of nutrition of preterm infants.
Unfortunately, in most cases, production of human milk
is inadequate or lactation is not established at all, in which
case nutrition with donor milk is appropriate choice [9,
10]. In all our subjects, MEN was conducted with human
donor milk, in which colostrum was used in five subjects.
The duration of MEN and further increase in volume
intake are also not precisely defined. There is a need for
a unique protocol considering increase in volume intake
which would have primarily practical role in everyday
neonatologist’s work [11]. In our subjects, MEN was
conducted over a period of days, with a volume of up to
25 mL/kg/day. After this time, an increase in volume in-
take was 15–20 mL/kg/day, adjusted to individual feeding
tolerance.
Measurements of body weight, body length, and head
circumference represent basic anthropometric indicators
of growth in the neonatal period. Skinfold thickness and
subscapular test are far less significant in neonatal clini-
cal practice, considering very small changes in neonates
[12]. Proper technique of measurement and adequately
trained personnel need to perform measurements in inter-
vals prescribed by the protocol or research methodology.
During this study, body weight was measured on digital
scales incorporated in incubators or on classic mechanical
scales (accuracy range ± 5 g). The proper way of measuring
body length is by using a stadiometer, but depending on
the clinical state of a patient, various forms of adapted flex-
ible plastic-coated tape measure are used. The use of tape
measure made from impregnated unstretchable cloth is the
most optimal way of measuring head circumference [13].
The time of birth weight achievement is also an indi-
rect indicator of nutritive support, and it is three weeks in
VLBW preterm infants, but according to clinical condition
it can be even longer [14]. Our subjects in whom MEN was
introduced early on reach birth weight on day 17, which
is significantly shorter compared to day 21 in group with
delayed enteral nutrition (p < 0.05).
Body weight gain during intrauterine growth is about
15–20 g/kg/day, while postnatal growth of 10–20 g/kg/
day is considered to be appropriate [15]. Average body
weight gain in the group with early introduced MEN was
10.88 g/kg/day, which is significantly more compared to
7.73 g/kg/day in the group with delayed enteral intake
(p < 0.05).
Increase in body length and occipitofrontal head cir-
cumference of 0.9 cm per week is ideal, and represents a
goal of adequate nutritive support, although this value is
far lower and harder to reach in clinical practice. Moni-
toring of early postnatal growth through series of body
length measurements in preterm infants shows a value of
0.5–0.9 cm per week, and occipitofrontal head circumfer-
ence of 0.5–1.1 cm per week [16, 17, 18]. Average weekly
gain in body length in our subjects was 0.45–0.58 cm, and
in head circumference 0.46–0.67 cm. The conducted study
wasn’t coherent considering the question of effect of mini-
mal enteral nutrition on short-term growth, while analysis
of long-term growth and its developmental effects was not
analyzed [19]. There is a need for new randomised stud-
ies that will include extremely low birth weight infants in
this research, as well as infants with intrauterine growth
restriction [20, 21].
CONCLUSION
Minimal enteral nutrition with human milk as an addition
to parenteral nutrition represent a very important practi-
cal approach in treatment of VLBW premature infants,
naturally stimulating the development of gastrointestinal
functions. Minimal enteral nutrition introduction within
72 hours compared to five or more days after birth signifi-
cantly contributes to the rate of body weight gain and to
earlier achievement of optimal nutritive intake, so it should
be practiced whenever possible.
NOTE
This paper is a part of a master’s thesis titled “Analysis
of the effect of minimal enteral nutrition on the growth
of very low birthweight premature infants,” defended on
February 18, 2014 at the School of Medicine, University
of Belgrade.
Marinković V. et al.
DOI: https://doi.org/10.2298/SARH160205024M

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Увод/Циљ Минимална ентерална исхрана (МЕИ) има битан
стимулативни ефекат на морфолошки и функционални раз-
вој гастроинтестиналног система код превремено рођеног
детета.
Циљ рада била је процена ефеката ране МЕИ на брзине
постизања оптималног ентералног нутритивног уноса и раст
телесне масе, телесне дужине и обима главе код превреме-
но рођене деце веома мале телесне масе (ВМТМ).
Методе рада Проспективном студијом је обухваћено 45
новорођенчади ВМТМ (1.010–1.450; 1.350 ± 305 g), 30 код
којих је МЕИ започет унутар три дана по рођењу и 15 код
којих је због хемодинамске и метаболичке нестабилности
ентерални унос започет након пет дана. Процена ефекта
ране МЕИ на брзину постизања оптималног нутритивног
уноса и раст основних антропометријских параметара за-
снивана је на поређењу са групом испитаника код којих је
ентерални унос започет касније.
Резултати Испитаници са рано започетом МЕИ у односу
на оне код којих је ентерална исхрана одложена су боље
напредовали у телесној маси (p < 0,05), брже достизали по-
рођајну телесну тежину (p < 0,05) и знатно раније успоста-
вљали оптимални ентерални унос (p < 0,05), док разлика у
расту телесне дужине и обима главе између ове две групе
испитаника није била значајна.
Закључак Рана МЕИ има знатан позитиван ефекат на брзину
пораста телесне тежине и раније успостављање оптималног
ентералног уноса код превремено рођене деце ВМТМ.
Кључне речи: новорођенчад веома мале телесне масе; рана
минимална ентерална исхрана; оптимални нутритивни унос
Утицај ране минималне ентералне исхране на раст и брзину постизања
оптималног нутритивног уноса превремено рођене деце веома мале телесне
масе
Весна Маринковић1, Нивеска Божиновић-Прекајски1, Милица Ранковић-Јаневски1, Зорица Јелић1, Весна Хајдарпашић1,
Недељко Радловић2,3,4
1Институт за неонатологију, Београд, Србија;
2Универзитетска дечја клиника, Београд, Србија;
3Универзитет у Београду, Медицински факултет, Београд, Србија;
4Академија медицинских наука Српског лекарског друштва, Београд, Србија
Eect of early introduction of minimal enteral feeding in very low birth weight preterm infants