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Feeding intolerance in preterm infants. How to understand the warning signs

Article  in  The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the
International Society of Perinatal Obstetricians · September 2011
DOI: 10.3109/14767058.2011.607663 · Source: PubMed

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 The Journal of Maternal-Fetal and Neonatal Medicine, 2011, 1-3, Early Online
Copyright © 2011 Informa UK, Ltd.
ISSN 1476-7058 print/ISSN 1476-4954 online
DOI: 10.3109/14767058.2011.607663
Review Article
Feeding intolerance in preterm infants. How to understand
the warning signs
Renato Lucchini, Bianca Bizzarri, Silvia Giampietro & Mario De Curtis
Dipartimento di Pediatria, “Sapienza” Università di Roma, Rome, Italy
It is essential to start enteral nutrition early to preterm infants
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by 93.40.127.238 on 09/06/11
by giving small amounts of milk (preferably human milk) to
ensure that metabolic homeostasis is kept stable and to limit
postnatal growth retardation. Increasing feeding volumes to
reach “full enteral feeding” is limited by individual feeding toler-
ance. Feeding intolerance is extremely common in premature
infants. The most frequent signs of a suspect feeding intolerance
are the presence of gastric residuals, abdominal distension and
the onset of crises of apnea/bradycardia. Gastric residuals are
probably a benign consequence of delayed gut maturation and
motility in VLBW infants and there are no established normal
standards. When gastric aspirates occur isolated they should
not immediately induce the neonatologist to withhold feeding.
For personal use only.
Gastric residual becomes more important when accompanied by
other warning signs, such as bilious vomiting, abdominal disten-
sion, abdominal wall erythema or ecchymosis, gross or occult
blood in the stool, apnoea, bradycardia and temperature insta-
bility. Nutrition protocols in preterm infants must take caution
when starting and increasing enteral feeding, and pay proper,
but not excessive, attention to early signs of food intolerance.
Keywords:  feeding intolerance, preterm infants
Appropriate nutrition plays a key role in the healthcare of preterm
infants. It is essential to give the newborn sufficient intakes since the
very early days to ensure that metabolic homeostasis is kept stable
and that postnatal growth retardation is as limited as possible.
The aim of nutritional programs is to provide as soon as
possible adequate nutrient intakes, preferably through the closest
physiological way, i.e., breastfeeding or bottle-feeding. However,
functional immaturity of the digestive metabolic system, which is
inversely related to gestational age, requires the protracted use of
parenteral nutrition and tube feeding (bolus or continuous).
The novel information and techniques available have changed
the approach of neonatologists to the nutritional problems of very
low birth weight (VLBW) infants. Parenteral nutrition is currently
the first choice approach in the first days of life and during critical
periods, given its effectiveness and safety. However, it is of para-
mount importance that enteral nutrition be started as soon as
possible, giving the premature baby small amounts of milk (pref-
erably human milk) at times and intervals, and using techniques
that take into account the specific features of each newborn and
the experience of the single unit.
There is increasing agreement that early enteral nutrition
should start by giving small amounts of milk to stable, low-risk
preterm infants (“minimal enteral feeding” or “trophic feeding”),
Correspondence: Renato Lucchini, Dipartimento di Pediatria, “Sapienza” Università di Roma. E-mail: renato.lucchini@uniroma1.it
1
but also to high-risk infants, albeit with a more cautious approach
[1]. Starting early enteral nutrition could promote functional
maturity of the gastrointestinal tract, provided this does not lead
to increased risk of disease. Increasing feeding volumes to reach
“full enteral feeding” is limited by individual feeding tolerance.
Preterm infants have often feeding difficulties for functional
immaturity of the gastrointestinal tract, which affects the motility
and the secretion of gut hormones.
Feeding tolerance is the ability of the newborn to ingest and
digest milk without complications, such as the inhalation of milk
in the respiratory tract, the onset or worsening of apneic episodes,
the onset of necrotizing enterocolitis (NEC), the most severe
intestinal disease of the newborn and a leading cause of death or
disability.
NEC is a severe inflammatory bowel disease that affects, almost
exclusively, premature infants. The pathogenesis of NEC is not
completely understood, but is likely multifactorial. NEC appears to
be an overreaction of the immune system to some type of insult
(ischemic, infectious, related to introduction of enteric feeds, or
a response to translocation of normal enteric bacteria) [2]. NEC
usually presents in the second week of life, after the start of enteral
feeding, but infants born at 23–28 weeks’ gestation can develop NEC
after several weeks of life, long after enteral feeding has begun.
Feeding intolerance is extremely common in premature
infants. Therefore it is important to know and assess correctly,
the warning signs of the possible complications of enteral
feeding. The most frequent signs of a suspect feeding intoler-
ance in preterm infants are the presence of gastric residuals and
abdominal distension.
There are no established normal standards for gastric residuals
in premature infants, although many empirical guidelines have
been issued by various sources. Gastric residuals are probably a
benign consequence of delayed gut maturation and motility in
VLBW infants. When aspirates occur in isolation, whatever their
colour, they should not immediately induce the neonatologist to
withhold feeds.
It is likely that larger residual volumes may be an early sign
of NEC (“pre-NEC)”, and VLBW infants who develop NEC have
more gastric residuals, but this increase is more marked only
immediately before the diagnosis [3].
Gastric residuals are the elements of feeding intolerance that
can be measured and compared most easily, although the magni-
tude of gastric residual that should be considered abnormal has
not been defined adequately to date. Some centres have empiri-
cally set gastric residual volumes at 2 mL in infants at ≤ 750 g
 2  R. Lucchini et al.
and 3 mL in infants from 750 to 1000 g, others have considered
volumes of more than one-third or 50% of feeds.
Some questions remain on how to behave when gastric resid-
uals occur. What is the proper response to an “at-risk” neonate?
Should it be no enteral feeding, and if so, for how long? Should
it be referred to the gastric residual volume, discard it, or reduce
the volume of the subsequent enteral feedings? To date we have
no definite answers. We need more scientifically-based investiga-
tions to help provide recommendations for safe, effective feeding
protocols for VLBW infants.
Gastric residual becomes more important when accompanied
by other warning signs, such as bilious vomiting, abdominal disten-
sion, abdominal wall erythema or ecchymosis, gross or occult
blood in the stool, apnoea, bradycardia and temperature instability.
Decreased bowel sounds suggest a reduced intestinal motility.
Abdominal distension is evident at the physical examination.
Abdominal girth can be measured, and an increase by more than
J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by 93.40.127.238 on 09/06/11
2 cm between the feeds is considered significant.
Abdominal X-rays provide information for both, a useful
diagnosis and the progression of the disease. Early radiographic
findings are dilated, gas-filled loops of bowel, air-fluid levels,
and thickened bowel walls. Pneumatosis intestinalis is the most
specific radiographic finding, suggesting a diagnosis of NEC.
Other highly suggestive findings include portal venous gas, pneu-
moperitoneum, fixed loops of bowel in serial films.
Caution is needed when starting and advancing feeding in
premature infants, to reduce the risk of disease; on the other
hand, delaying the start of enteral feeding results in prolonged
parenteral nutrition, and increases the risk of the related compli-
For personal use only.
cations, such as infections and cholestasis.
Most authors suggest to start enteral feeding early, in the first
few days of life, with trophic feeding, defined as about 1 mL/kg/h,
without increasing the amount too soon at first, and advancing
reasonably rapidly thereafter. This field is still controversial; in
fact, according to a Cochrane review, there is insufficient data to
prove the safety of this approach, although its important benefits
cannot be neglected. However, the review took into account only
five trials with a total of 600 participants, most of them with intra-
uterine growth retardation [4].
A paper published in 2003, one of the largest controlled
randomized trials of trophic versus advancing feeds, was closed
early because an excess of infants assigned to advancing feeding
volumes developed NEC [5]. This study generated much discus-
sion. However, enteral feeds were started late, around the 10th day,
in both groups and those who underwent advanced feeding had
received lower percentages of antenatal steroids. In a recent case-
control study comparing VLBW who developed NEC to those who
did not, cases had shorter duration of trophic feeding, and were
fully fed, significantly earlier than controls [6]. However, another
study comparing 1000–1499 g infants in whom feed volume was
advanced to 30 mL/Kg/d versus those in whom it was advanced to
20 mL/Kg/d showed that infants with rapid advancing of enteral
feeding achieved full enteral feeding earlier, regained birth weight
earlier (an average of 5 days before) and had a shorter hospital
stay, without an increased risk of NEC, feed interruption or feed
intolerance [7].
Another sign of feeding intolerance that frequently leads to
a temporary suspension of enteral feeding is the onset of crises
of apnea/bradycardia and possible inhalation of milk into the
airways, associated with gastroesophageal reflux (GER).
In preterm infants there are three to five events of gastroesoph-
ageal reflux per hour. The main mechanism of reflux episodes is
transient lower esophageal sphincter relaxation due to the decrease
in pressure, unrelated to swallowing, which allows gastric material
to enter the esophagus. The higher incidence of GER in newborns,
especially in preterms, is determined by several favoring factors;
supine body position (the gastroesophageal junction is continu-
ally submerged in gastric contents), daily high volume of fluid (an
intake of 180 mL/Kg/d corresponds to almost 14 L/d in adults),
immature central autonomic neural pathways and feeding tubes
(which impair the continence of the lower esophageal sphincter).
The upper esophageal sphincter function appears to be well
developed by 33 weeks gestational age and esophageal clearance
mechanisms are effective by 31 weeks.
Currently the most accurate technique in the evaluation of
reflux episodes is multichannel intraluminal impedance (MII)
which helps identify a precise temporal relationship between
apnea of prematurity and GER.
Apnea is defined as the cessation of breathing for over
20 seconds or a period of shorter duration (at least 5 seconds)
if associated with significant desaturation or bradycardia. Apnea
is traditionally classified as central (due to the immaturity of
breath control systems), obstructive (characterized by ineffec-
tive respiratory efforts due to immature control system of the
airways) or mixed.
In particular, obstructive apnea may be caused by several
mechanisms that lead to the closure of the glottis; esophageal
distention by reflux episodes without upper esophageal sphincter
relaxation, activation of epiglottal chemoreceptors by nonsaline
fluid (water or milk) at the anterior margin of the glottis, and acti-
vation of laryngeal chemoreceptors.
The relationship between GER and apnea of prematurity
remains controversial. Apneic episodes in preterm infants occur
frequently in the immediate postprandial period, when GER is
most likely to occur. Indeed a recent study of 36 preterm infants,
who were referred for MII and 12 hours apnea evaluation, proved
that more GER events occurred after a feed than before, but the
rates of apnea, bradycardia and desaturations were not altered by
infant feeding. Moreover after feeds, the reflux was less acidic and
flowed higher up the esophagus [8].
Di Fiore et al demonstrated that GER has no effect on the dura-
tion or severity of cardiorespiratory events; in 71 preterm infants
less than 3% respectively of apnea, desaturations and bradycardia
events were preceded by GER, and apnea episodes associated with
reflux had a shorter duration [9]. According to other authors there
is a temporal relationship between GER and apnea of prematu-
rity: in 26 preterm infants, who were referred for 6 hours MII and
polysomnography, the frequency of apnea within 30 seconds after
GER, was higher than detected in the 30 seconds before; apnea
episodes seemed to be related to non acid GER [10].
In conclusion, nutrition protocols in preterm infants, which
aim to maintain a growth rate similar to that occurring in
the corresponding intrauterin period, must take into account
the digestive-metabolic capacity of the single subject, taking
caution when starting and increasing enteral feeding, and
paying proper, but not excessive, attention to early signs of food
intolerance.
Declaration of interest: Authors declare no conflict of interest.
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Copyright © 2011 Informa UK, Ltd.
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