Literature Review

Nonpharmacological Management of Gastroesophageal Reflux in Preterm Infants

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DOI: 10.1155/2013/141967 · Source: PubMed
Cite this publication
Abstract
Gastroesophageal reflux (GOR) is very common among preterm infants, due to several physiological mechanisms. Although GOR should not be usually considered a pathological condition, its therapeutic management still represents a controversial issue among neonatologists; pharmacological overtreatment, often unuseful and potentially harmful, is increasingly widespread. Hence, a stepwise approach, firstly promoting conservative strategies such as body positioning, milk thickening, or changes of feeding modalities, should be considered the most advisable choice in preterm infants with GOR. This review focuses on the conservative management of GOR in the preterm population, aiming to provide a complete overview, based on currently available evidence, on potential benefits and adverse effects of nonpharmacological measures. Nonpharmacological management of GOR might represent a useful tool for neonatologists to reduce the use of antireflux medications, which should be limited to selected cases of symptomatic babies.
Hindawi Publishing Corporation
BioMed Research International
Volume 2013, Article ID 141967, 7 pages
http://dx.doi.org/10.1155/2013/141967
Review Article
Nonpharmacological Management of Gastroesophageal Reflux
in Preterm Infants
Luigi Corvaglia,
1,2
Silvia Martini,
1
Arianna Aceti,
1
Santo Arcuri,
1,2
Roberto Rossini,
1,2
and Giacomo Faldella
1,2
1
Neonatology and Neonatal Intensive Care Unit, S. Orsola-Malpighi Hospital, Via Massarenti 11, 40138 Bologna, Italy
2
Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Via Massarenti 9, 40138 Bologna, Italy
Correspondence should be addressed to Luigi Corvaglia; luigi.corvaglia@unibo.it
Received 29 April 2013; Accepted 25 July 2013
Academic Editor: Jonathan Muraskas
Copyright © 2013 Luigi Corvaglia et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Gastroesophageal reux (GOR) is very common among preterm infants, due to several physiological mechanisms. Although
GOR should not be usually considered a pathological condition, its therapeutic management still represents a controversial issue
among neonatologists; pharmacological overtreatment, oen unuseful and potentially harmful, is increasingly widespread. Hence,
a stepwise approach, rstly promoting conservative strategies such as body positioning, milk thickening, or changes of feeding
modalities, should be considered the most advisable choice in preterm infants with GOR. is review focuses on the conservative
management of GOR in the preterm population, aiming to provide a complete overview, based on currently available evidence, on
potential benets and adverse eects of nonpharmacological measures. Nonpharmacological management of GOR might represent
a useful tool for neonatologists to reduce the use of antireux medications, which should be limited to selected cases of symptomatic
babies.
1. Introduction
Gastroesophageal reux (GOR) is common in preterm
infants, with a 22% estimated incidence in babies born
before 34 weeks of gestation [1]. Several factors may con-
tribute to its development: relatively abundant milk intakes,
the supine posture which promotes the passage of liquid
gastric content into oesophagus, the immature oesophageal
motility, and the subsequent poor oesophageal clearance of
reuxate [2]. Hence, in the preterm population GOR is due
to several physiological mechanisms, and it should not be
usually considered as pathological. However, in moderate to
severe cases, GOR may lead to complications, such as lung
aspiration, esophagitis, feeding problems, and failure to thrive
[3], therefore prolonging hospital stay [4]; its linkage with
apnoeas [5]orchroniclungdisease[68]isstillondebate.
e therapeutic management of GOR still represents
a controversial issue among neonatologists. A stepwise
approach, promoting at rst nonpharmacological interven-
tions such as body positioning, milk thickening, or mod-
ications in feeding modalities, should be considered the
mostadvisablechoicetomanageGORinpreterminfants[3,
5, 9]; this would allow avoiding pharmacological treatment,
which could be limited to those infants who do not benet
from conservative measures or who experience GOR clinical
complications [10].
In recent years, however, the empiric use of antireux
medications, both during hospital stay in Neonatal Intensive
Care Unit (NICU) and aer discharge [11], has substantially
increased. Pharmacological therapies have been shown to
increase the risk of serious adverse eects in the neona-
tal population: the use of gastric acid inhibitors, that is,
histamine-2 (H2) blockers and proton pump inhibitors (PPI),
has been recently linked to increased rates of necrotizing
enterocolitis (NEC) [12, 13] and infections (overall infections,
sepsis, pneumonia, and urinary tract infections) [14], whereas
cisapride administration was proven to provoke a relevant
prolongation of QTc [15, 16].
Specic diagnostic investigations should be performed
before treatment, in order to assess GOR features, because
the prevalence of acid or nonacid GORs has dierent clinical
and therapeutic implications. Specically, acid reux, which
2 BioMed Research International
occurs predominantly in the late postprandial period [17], is
reported to play a relevant role in the development of gas-
troesophageal reux disease (GORD) [2], whereas nonacid
reux, which is more frequent during the early postprandial
period [17],hasbeenproposedasapotentialtriggerforGOR-
related apnoeas in the preterm population [18]. It should
be also considered that many pharmacological therapies
act specically on acid GOR, while dierent conservative
strategies have dierent eects on acid and nonacid GORs.
Due to its ability to both detect acid, weakly acid, and
alkaline GORs [17] and assess the physical nature (gaseous,
liquid, or mixed) of reux episodes, combined multiple
intraluminal impedance (MII) and pH monitoring is highly
eective in detailing GOR features, being superior to pH-
metry and MII alone. It is currently considered the best
choice to diagnose GOR [3, 19] and to evaluate the ecacy of
antireux therapy [20]. Additionally, a reux scoring system
basedonclinicalobservationandsuitedforhospitalized
preterm infants has been recently developed for GOR diagno-
sis and management [3]; this questionnaire, however, cannot
replace standard diagnostic investigations and needs further
validation.
is review focuses on conservative management of GOR
in preterm infants, aiming to provide a complete overview
on potential benets and adverse eects of currently available
nonpharmacological measures.
2. Body Positioning
Body positioning is widely used as a conservative approach to
manage GOR in hospitalized preterm infants [1]. Since 1982,
when a decrease of GOR was noted in prone neonates [21],
several trials tested the ecacy of dierent body positions on
GOR indexes in both term and preterm infants.
e rst study on preterm infants dates back to 1999,
when Ewer et al. [22]foundarelevantimprovementinacid
reux indexes (frequency, reux index, number of reuxes
longer than 5 minutes, and duration of the longest episode)
at pH monitoring in both prone and le-side positions. e
eectiveness of prone position was later conrmed by Bhat et
al. [23], who examined by means of pH monitoring a cohort
of healthy preterm infants before discharge. Omari et al. [24]
combined oesophageal manometry and MII to investigate the
ecacy of le versus right lateral position on GOR features
in healthy preterm infants; le-side positioning resulted in a
signicant decrease of transient lower oesophageal sphincter
relaxations (TLOSRs), which are known to be the main
triggering mechanisms for GOR episodes, whereas right
lateral position was associated with a higher number of
TLOSRs and liquid reuxes [25].
While pH monitoring is not eective in detecting nonacid
GORs, MII alone cannot distinguish between acid and
nonacid reuxes; hence, we assessed the eects of body
positioning on both acid and nonacid GORs in preterm
symptomatic infants combining MII and pH monitoring
(pH-MII) [26]. Lower acid and nonacid GOR indexes were
observed in both prone and le lateral positions. Particularly,
le-side positioning led to a signicant decrease of acid GOR
episodes during the earlier postprandial period (up to 1 hour
and 30 minutes aer meal), while the prone posture was more
eective to reduce acidic oesophageal exposure in the late
postprandial period.
In conclusion, body positioning can be considered an
eective strategy to manage both acid and nonacid GORs in
preterm infants; improvements of GOR indexes are observed
in prone and le lateral positions, whereas supine and right
lateral positioning seem to play a worsening eect. However,
due to the established risk of sudden infant death syndrome
(SIDS) linked to prone positioning [27], this measure is
limited to hospitalized babies and should not be applied
in symptomatic infants discharged without cardiorespiratory
monitoring.
Placingthebabiesonahead-upslopeisameasure
frequently adopted in clinical practice [1]. However, head
elevationresultedtobeineectivetoreduceacidGORin
both prone and supine positions [28, 29]; furthermore, the car
seat positioning was found to elicit acid GOR exacerbations
[30]. Data on preterm infants, however, are currently lacking.
Hence, on the basis of the available evidence, head rising
should not be considered an eective strategy to reduce GOR
in term infants up to six months of life.
3. Feeding Strategies
Feeds frequency (every two, three, or four hours), as well as
dierent feeding modalities, are thought to inuence GOR
features.
e relationship between feeds frequency and GOR
episodes in both term and preterm infants was investigated at
rst by Omari et al. [2], who observed a positive correlation
between the frequency of feedings and the occurrence of
nonacid GOR episodes, with a concomitant decrease in the
number of acid GOR, which is known to be determinant
for the development of GORD [31]. According to the results
of this study, it can be hypothesised that frequent, small-
volume feeds probably reduce GOR in mildly symptomatic
infants with prolonged oesophageal acid exposure but have
no benet for symptomatic babies with predominant nonacid
GOR.
Bolus and continuous tube feedings are the most com-
mon enteral feeding techniques in NICUs. Clinical practice
suggests that changing the feeding method (i.e., shiing
from bolus to continuous feeding or vice versa) may rep-
resent an eective conservative approach in neonates with
symptomatic GOR [3]. Indeed, the permanence of a tube
through lower oesophageal sphincter (LOS) is shown to
aect the occurrence of GOR [32], while the sudden gastric
distension determined by bolus administration can impair
LOS continence, thus favouring GOR [5, 33, 34].
e eect of dierent feeding strategies on GOR in a
preterm cohort has been recently assessed by Jadcherla et al.
[35] by means of pH-MII. A signicant negative correlation
between feeding duration and total GOR events, number
of nonacid GORs, and time of oesophageal bolus clearance
was observed. Consistently with this nding, lowered feeding
ow rates (mL/min) yielded a decrease in the same GOR
BioMed Research International 3
features. us, the reduction of feeding ow rate, which
results in a prolonged feeding duration, seems to represent
a potentially useful strategy for GOR management, especially
in those infants with predominant nonacid GOR. However,
further trials are needed to conrm these preliminary data.
4. Feed Thickening
ickened feeds, that is, human milk or formula added
with thickening agents or commercial antiregurgitation (AR)
formulas, are increasingly being used as nonpharmacological
treatments of GOR in symptomatic infants [1].
In 2008, Horvath et al. systematically evaluated data
from randomized controlled trials performed in term infants
on the ecacy of thickened formulas on GOR features,
detected with pH monitoring. Despite a signicant decrease
of symptoms as regurgitations and vomiting and an increase
in daily weight gain, thickening agents were ineective in
reducing acid GOR indexes [36]. An improvement of acid
GORfeaturesininfantsfedacornstarchthickenedformula
hasbeenreportedinonlyonetrial[37]. As for nonacid GOR,
a remarkable reduction of reux episodes, mean oesophageal
reux height, and frequency of regurgitation was observed by
Wenzl et al. in association with the use of a galactomannan-
thickened formula [38].
Further investigations in larger controlled trials are
needed in order to investigate the safety prole of thickening
agents. So far, an increase in coughing was noticed in symp-
tomatic babies fed on rice-thickened formulas [39], and a
case of an allergic reaction linked with carob gum thickening
has been described [40]. Moreover, despite that infants fed
formulas thickened with indigestible carbohydrate showed
normal growth and nutritional parameters at a 3-month
follow-up study [41], the use of carob bean gum, evaluated
invitro,wasreportedtoaecttheintestinalabsorptionof
calcium, iron, and zinc more than thickening with digestible
carbohydrates [42].
With regard to the preterm population, only a small
number of studies on the eectiveness and the safety of
thickening agents are currently available. We have previously
investigated the ecacy of fortied human milk thickened
with precooked starch in a small cohort of preterm symp-
tomatic infants: no improvement in the rates of both acid and
nonacid GORs was documented; additionally, a trend toward
an increase of the total number of GORs was observed. To
the best of our knowledge, this was the rst study testing the
eectiveness of thickened human milk in preterm infants;
on the basis of these preliminary results, starch-thickening
of fortied human milk does not appear to be an advisable
strategy to reduce GOR in preterm symptomatic infants
[43]. Furthermore, a linkage between milk thickening and
NEC development has been recently suggested [44, 45];
hence, milk thickening in the preterm population is not
recommended before an adequate achievement of feeding
tolerance [3].
Commercial thickened formulas are inadequate for the
nutritional needs of preterm infants, due to their lower
caloric and protein contents and to the lack of long-chain
polyunsaturated fatty acids (LCPUFA), which play a relevant
role in the structural development of retinal membranes and
central nervous system (CNS). In our previous study, a starch-
thickened formula tailored on preterms nutritional needs
was specically designed to investigate its ecacy on GOR
features in symptomatic preterm infants [46]. e thickened
formula, however, was found to be ineective on nonacid
GOR features, evaluated by means of combined pH-MII. is
result might be explained by the properties of the amylopectin
component, which increases its viscosity at an acid gastric
pH, being thereby eective during the late postprandial
period,whennonacidGORdoesnotprevail[17]. Despite
the signicantly lowered rate of acid GORs, the thickened
formulafailedtoreducethemeanoesophagealacidexposure,
which is known to be the main determinant index for the
development of GORD [31]. Moreover, when compared to a
standard preterm formula, this thickened formula yielded a
longer duration of acid GOR episodes, which was probably
due to a slower oesophageal clearance. ere are no data on
the safety of thickened formulas in preterm infants. Hence, as
well as human milk thickening, formula thickening seems to
be ineective to reduce GOR in symptomatic preterm infants.
Nevertheless, larger controlled trials might be advisable to
conrm these preliminary ndings and to assess the safety
of thickened formulas in the preterm population.
5. Hydrolysed Formulas
Hydrolysed protein formulas (HPFs) are reported to reduce
gastrointestinal transit time [47], to increase stool frequency
[48], and to improve feeding tolerance, therefore leading to
an earlier achievement of full enteral feeding [49]. Several
mechanisms through which HPFs could act have been pro-
posed [50]; whereas some evidence suggests that HPFs elicit a
higher motilin release than standard preterm formulas (SPFs)
[51], a study performed on animals has shown that protein
hydrolysis diminishes the activity of milk protein-derived
opioid receptor agonists (𝛽-casomorphins) [52]. e eect of
HPFs on gastric emptying, though, is still controversial; while
some authors found an improvement [47, 53], others found
no dierence between HPFs and SPFs [54].
Extensively HPFs (eHPFs) have been shown to improve
GOR features in term infants and children symptomatic
for GOR [55]. Sensitized infants with cow’s milk allergy
(CMA) are known to develop gastric dysrhythmia, which
can lead to a severe impairment of gastric motor function
and delayed gastric emptying, thereby contributing to GOR
exacerbation [56, 57]. For this reason, infants with CMA
are more likely to suer from symptoms as regurgitation
and vomiting, which appear to be indistinguishable from
physiological GOR. us, when own mother’s milk is not
available, the dietary management of GOR recommended in
the recent guidelines by the European Society of Pediatric
Gastroenterology, Hepatology, and Nutrition includes a 2–4-
weektrialofeHPForaminoacidbasedformula[20].
Inarecenttrial,wehavecomparedtheecacyofaneHPF
versus a SPF on GOR features in preterm infants symptomatic
for both GOR and feeding intolerance. A signicant decrease
4 BioMed Research International
in total acid GOR episodes and reux index was observed in
newborns fed the eHPF, whereas no dierence between the
two formulas was found in terms of GOR height and nonacid
GOR features [58]. Acid GORs being more frequent in the
late postprandial period, the reduction in acid GOR could be
attributed to the enhancement of gastric emptying previously
reported in premature infants fed eHPFs [47]. is is the
rst study aiming to evaluate the ecacy of eHPFs on GOR
features in preterm infants. According to our preliminary
ndings, eHPFs are eective in decreasing acid GOR in
preterm infants experiencing symptoms of GOR and feeding
intolerance. However, the sample size was small, leading to
a low power to evaluate the clinical ecacy of the eHPF on
GOR symptoms. Furthermore, it should be considered that
the nutritional characteristics of the majority of eHPFs are
generallyinadequateforthehighnutritionalneedsofpreterm
infants. erefore, further larger trials should be carried out
to conrm the ecacy of a nutritionally adequate eHPF in
reducing acid GOR features and improving GOR clinical
symptoms in the preterm population.
6. Human Milk Fortifiers and Human Milk
Protein Content
In order to achieve the nutritional needs of preterm infants,
human milk is usually supplemented with commercial
human milk fortiers (HMFs), which contain proteins, car-
bohydrates, and minerals. As stated in a systematic review
[59], preterm infants fed fortied HM have improved weight
gain, linear growth, and head circumference growth without
experiencing major adverse eects (i.e., necrotising entero-
colitis). On the other hand, HM fortication might lead
to feeding intolerance, because it increases osmolality to
values higher than the expected, with further increase over
time [60]. Moreover, a worsening of acid GOR related to
an increase in the osmolality of meals has been previously
demonstrated in infants and children [61].
We have previously evaluated whether standard fortica-
tion with dierent amounts of HMFs (the low dose being 3%
and the higher 5%) may aect GOR features in symptomatic
preterm infants [62]. e standard addition of both HMF 3%
and HMF 5% led to a signicant increase of nonacid GORs,
nonacid reux index, and oesophageal height of reux, while
no dierence was observed in acid GOR features.
So far, this is the rst study to explore the eect of
HMFs on GOR features in preterm infants; therefore, these
preliminary data, obtained from a relatively small population,
need to be validated in larger clinical trials.
7. Intragastric Tubes
Due to the inability of preterm infants to coordinate sucking,
swallowing,andbreathing,tubefeedingisfrequentlyused
in NICUs. However, the presence of a tube through the
gastroesophageal junction can exacerbate GOR through two
dierent mechanisms: rstly, weakening the competence of
LOS and subsequently enhancing the reuxate of gastric
content into the oesophageal lumen [63] and, secondly,
impairing oesophageal clearance [64]. Consistently with this
assumption, Peter et al. [32] found a higher incidence of GOR,
especially aer the rst postprandial hour, in a small cohort
of preterm infants who had the MII catheter placed through
the gastroesophageal junction. A similar study, evaluating
the impact of two dierent nasogastric tubes on GOR in
term neonates and older infants, found no eect with the
smaller tube (8 F) but an increase of GOR in association
with the larger one (12 F) [64]. Conversely, two trials [35, 65]
evaluating tube versus oral feeding in symptomatic term and
preterm infants found a signicantly lower rate of GORs
inthetube-fedgroup;thisoppositeresultmightbedueto
some methodological dierences between the studies such
as, for instance, the tube size or the removal of the feeding
tube during the postprandial period. To avoid potential
eects related to the presence of an intragastric tube in
infants with GOR unable to bottle-feed, the withdrawal of
thefeedingtubeaerbolusadministrationmightrepresent
afeasiblestrategy[32]; however, before being recommended,
this practice should be tested in a larger, randomized trial, in
order to weigh the potential advantages against side eects
(i.e., oesophageal irritation).
8. Pacifier Usage
Nonnutritive sucking (NNS) inuences gastrointestinal func-
tions of preterm infants, increasing the sucking reex mat-
uration and endorsing an earlier achievement of full oral
feeding [66]; moreover, NNS is reported to slow down the
intestinal transit time and to enhance weight gain [67],
whilenoeectswereobservedongastricemptyingand
nutrient absorption [68, 69].Ahighernumberofswallows
are observed during NNS. It has been previously documented
that swallowing elicits LOS relaxation, which is known to
exacerbate the rise of gastric content into the oesophagus
[70]. At the same time, however, the act of swallowing
seems to promote the oesophageal clearance of reuxate [71];
therefore, a possible role of NNS on gastroesophageal reux
might be hypothesized.
e rst study evaluating the role of NNS on GOR was
performed by Orenstein in 1988. Term infants younger than
6 months using a pacier underwent pH monitoring [72];
NNS was reported to inuence only the frequency of GOR
episodes, which was increased in the prone position and
decreased in the seated position. is controversial nding,
however, cannot be applied to premature babies.
So far, the ecacy of NNS by means of a pacier on
preterm infants with symptomatic GOR has been investigated
only by Zhao et al. [73], who reported a faster gastric
emptying as well as a reduction of GOR features (number of
reuxes, reux index, and total time at pH <4)ininfants
receiving NNS; however, as GOR episodes were detected by
a pH probe, the eect of NNS on nonacid GOR was not
evaluated. us, further studies are needed to clarify the role
of pacier usage in preterm infants with pathologic GOR.
BioMed Research International 5
9. Conclusions
Gastroesophageal reux is a common and mainly physi-
ological condition in preterm infants. Although evidence
currently available on the conservative management of GOR
is still limited, a stepwise approach, with nonpharmacological
strategies as the rst-line treatment, is advisable in infants
experiencing noncomplicated GOR. On the basis of the exist-
ing literature, body positioning can be considered the most
established and safe treatment. Le-side and prone positions
are eective in reducing both acid and nonacid GORs but
should be limited to hospitalized preterm infants due to the
higher risks of SIDS. Improvements can also be obtained by
dietary changes; particularly, a prolonged feeding duration
seems to be eective in infants with predominant nonacid
GOR, whereas symptomatic babies with acid GOR might
benet from frequent, small feeds. Extensively hydrolysed
formulas are found to improve acid GOR features, while both
formulaandhumanmilkthickeningresultedtobeineective
and potentially harmful. Finally, the role of nonnutritive
sucking and intragastric tubes is still controversial, thereby
needing to be further investigated in larger trials.
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  • ... and reassurance for uncomplicated GOR. Giving small frequent feeds is commonly used but may be impractical and may even increase the number of reflux episodes due to a shorter post-prandial time (3). Although placing infants in the prone or left lateral position improves GOR, this cannot be recommended in infants without cardio-respiratory monitoring due to risk of sudden infant death syndrome (3). ...
    ... Giving small frequent feeds is commonly used but may be impractical and may even increase the number of reflux episodes due to a shorter post-prandial time (3). Although placing infants in the prone or left lateral position improves GOR, this cannot be recommended in infants without cardio-respiratory monitoring due to risk of sudden infant death syndrome (3). There is also insufficient evidence to support head-up positioning in reducing GOR (3). ...
    ... Although placing infants in the prone or left lateral position improves GOR, this cannot be recommended in infants without cardio-respiratory monitoring due to risk of sudden infant death syndrome (3). There is also insufficient evidence to support head-up positioning in reducing GOR (3). ...
  • ... Giving small frequent feeds is commonly used but may be impractical and may even increase the number of reflux episodes due to a shorter post-prandial time. 3 Although placing infants in the prone or left lateral position improves GOR, this cannot be recommended in infants without cardiorespiratory monitoring due to risk of sudden infant death syndrome. 3 There is also insufficient evidence to support head-up positioning in reducing GOR. 3 Pharmacological management should be reserved for infants who fail to respond to conservative approaches. ...
    ... 3 Although placing infants in the prone or left lateral position improves GOR, this cannot be recommended in infants without cardiorespiratory monitoring due to risk of sudden infant death syndrome. 3 There is also insufficient evidence to support head-up positioning in reducing GOR. 3 Pharmacological management should be reserved for infants who fail to respond to conservative approaches. ...
    ... 3 There is also insufficient evidence to support head-up positioning in reducing GOR. 3 Pharmacological management should be reserved for infants who fail to respond to conservative approaches. ...
  • ... Preterm infants are at risk for gastroesophageal reflux because of physiological immaturity of the lower esophageal sphincter, impaired esophageal peristalsis, relatively abundant milk intake, and slower gastric emptying. [14][15][16][17] The estimated incidence of gastroesophageal reflux in infants born less than 34-week gestation is approximately 22%. 16 Several studies have shown that there is a subgroup of infants with cow's milk protein allergy who present with regurgitation and vomiting: symptoms that are indistinguishable from gastroesophageal reflux. ...
    Article
    Background: Gastroesophageal reflux is a common disorder in pediatrics. Clinicians should be familiar with the proper evaluation and management of this condition. Objective: To provide an update on the current understanding, evaluation, and management of gastroesophageal reflux in children. Methods: A PubMed search was performed with Clinical Queries using the key term 'gastroesophageal reflux'. The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, and reviews. The search was restricted to the English literature and the pediatric age group. Results: Regurgitation is the most frequent symptom of gastroesophageal reflux and is present in nearly all cases. Gastroesophageal reflux occurs normally in infants, is often physiological, peaks at 4 months of age, and tends to resolve with time. Gastroesophageal reflux disease occurs when gastric contents reflux into the esophagus or oropharynx and produce troublesome symptom(s) and/or complication(s). A thorough clinical history and a thorough physical examination are usually adequate for diagnosis. When the diagnosis is ambiguous, diagnostic studies may be warranted. A combined esophageal pH monitoring and multichannel intraluminal esophageal electrical impedance device is the gold standard for the diagnosis of gastroesophageal reflux disease if the diagnosis is in doubt. In the majority of cases, no treatment is necessary for gastroesophageal reflux apart from reassurance of the benign nature of the condition. Treatment options for gastroesophageal reflux disease are discussed. Conclusion: In most cases, no treatment is necessary for gastroesophageal reflux apart from reassurance because the condition is benign and self-limiting. Thickened feedings, postural therapy, and lifestyle changes should be considered if the regurgitation is frequent and problematic. Pharmacotherapy should be considered in the treatment of more severe gastroesophageal reflux disease for patients who do not respond to conservative measures. Proton pump inhibitors are favored over H2-receptor antagonists because of their superior efficacy. Antireflux surgery is indicated for patients with significant gastroesophageal reflux disease who are resistant to medical therapy.
  • ... Putting neonates in proper position (positing) during feeding and afterwards is one of these cares (7) . The common positions in the ICU of neonates, includes lateral sleeping, supine and prone (10) . Usually after gavage, in order to reduce the risk of aspiration and reflux, they put the neonate in prone or right lateral sleeping position (9) . ...
  • ... Pengaturan posisi pronasi dapat menurunkan frekuensi muntah dan kejadian desaturasi pada BBLR. Kejadian muntah dan desaturasi pada BBLR yang mengalami intoleransi pemberian minum enteral disebabkan karena imaturitas pada lower esophageal sphinter atau LES (Carvaglia et al., 2013). Pada bayi prematur terjadi relaksasi pada LES, sehingga meningkatkan tekanan intragastrik dan terbentuk rongga antara lambung dan esofagus. ...
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    Full-text available
    Introduction: Enteral feeding intolerance is a common problem in low birth weight infants. This study aimed to analyze the effects of sleep positioning on low birth weight infants on the occurrence of enteral feeding intolerance. Methodology: This quasi experiment was applied on 20 low birth weight infants with a purposive sampling technique. The infants were grouped into control and intervention. Infants in the control group were given intervention with routine procedures; while those in the intervention group were performed prone sleep positioning after enteral feeding with the head of the bed elevated 30 degrees during the enteral feeding. Results: Independent t-test and Fisher’s Exact Test analysis showed that sleep positioning could decrease desaturation event (p value = 0.011), abdominal distension (p value = 0.017), and frequency of vomiting (p value = 0.035). Discussion: Nurses can make sleep positioning as standard operating procedures in low birth weight infants who have enteral feeding intolerance
  • Chapter
    Gastroösophagealer Reflux bedeutet ein Zurückfließen von Mageninhalt in den Ösophagus. Das Phänomen kann physiologischerweise erfolgen oder aber gravierende gesundheitliche Konsequenzen für den Patienten nach sich ziehen. In letzterem Falle spricht man von pathologischem gastroösophagealem Reflux. Dieser äußert sich unterschiedlich in den verschiedenen Altersgruppen. Einige kinderchirurgische Erkrankungen und angeborene Fehlbildungen prädisponieren zum Auftreten eines pathologischen gastroösophagealen Refluxes. Wenn konservative Maßnahmen die Symptome nicht unter Kontrolle bringen, ist eine chirurgische Therapie indiziert. Dabei gibt es verschiedene Ansätze, darunter zum einen eine partielle oder eine vollständige Fundoplikatio. Wenn die Indikation zur Fundoplikatio gestellt wird, sollte diese nach Möglichkeit laparoskopisch erfolgen. Der Eingriff geht mit einem nicht unerheblichen Rezidivrisiko einher. Allerdings kann unbehandelter gastroösophagealer Reflux langfristig ebenfalls zu schwerwiegenden Komplikationen wie einem Barrett-Ösophagus, einer Striktur oder zu einem Speiseröhrenkarzinom führen.
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    Full-text available
    Background: Gastroesophageal reflux is a common condition among premature infants, which causes problems such as reduced weight gain and prolonged length of hospital stay. Body status is an appropriate way to reduce this condition. However, there have been few studies conducted in this regard. The objective of this study was therefore to investigate the effect of body status on gastroesophageal reflux in premature infants. Methods: The present research was a crossover study conducted on premature infants with a gestational age of 33-36 weeks in Al-Zahra Hospital in Tabriz, Iran, from January to March 2015. In this clinical trial, thirty-two premature infants hospitalized in this center were selected as the sample. The initial selection of the participants was based on the simple random sampling. Then the participants were allocated to groups using randomized block procedure. Each infant was under study for 4 days. After each feeding and about two hours before the beginning of next feeding, the infants were randomly and not repeatedly put in one of the following four status for 12 hours (8 am -8 pm) every day: facilitated fetal tucking posture in lateral position, free body posture in lateral position, facilitated fetal tucking posture in supine position, and free body posture in supine position. Then, the incidence of gastroesophageal reflux was measured in each of these statuses. SPSS software, version 21 (SPSS Inc., Chicago, IL, USA) was used to analyze the data at significant level of P
  • Article
    Full-text available
    Background: Gastro-oesophageal reflux (GOR) is common in infants, and feed thickeners are often used to manage it in infants as they are simple to use and perceived to be harmless. However, conflicting evidence exists to support the use of feed thickeners. Objectives: To evaluate the use of feed thickeners in infants up to six months of age with GOR in terms of reduction in a) signs and symptoms of GOR, b) reflux episodes on pH probe monitoring or intraluminal impedance or a combination of both, or c) histological evidence of oesophagitis. Search methods: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2), MEDLINE via PubMed (1966 to 22 November 2016), Embase (1980 to 22 November 2016), and CINAHL (1982 to 22 November 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials. Selection criteria: We included randomised controlled trials if they examined the effects of feed thickeners as compared to unthickened feeds (no treatment or placebo) in treating GOR in term infants up to six months of age or six months of corrected gestational age for those born preterm. Data collection and analysis: Two review authors independently identified eligible studies from the literature search. Two review authors independently performed data extraction and quality assessments of the eligible studies. Differences in opinion were resolved by discussion with a third review author, and consensus was reached among all three review authors. We used the GRADE approach to assess the quality of the evidence. Main results: Eight trials recruiting a total of 637 infants met the inclusion criteria for the systematic review. The infants included in the review were mainly formula-fed term infants. The trials were of variable methodological quality. Formula-fed term infants with GOR on feed thickeners had nearly two fewer episodes of regurgitation per day (mean difference -1.97 episodes per day, 95% confidence interval (CI) -2.32 to -1.61; 6 studies, 442 infants, moderate-certainty evidence) and were 2.5 times more likely to be asymptomatic from regurgitation at the end of the intervention period (risk ratio 2.50, 95% CI 1.38 to 4.51; number needed to treat for an additional beneficial outcome 5, 95% CI 4 to 13; 2 studies, 186 infants, low-certainty evidence) when compared to infants with GOR on unthickened feeds. No studies reported failure to thrive as an outcome. We found low-certainty evidence based on 2 studies recruiting 116 infants that use of feed thickeners improved the oesophageal pH probe parameters of reflux index (i.e. percentage of time pH < 4), number of reflux episodes lasting longer than 5 minutes, and duration of longest reflux episode. No major side effects were reported with the use of feed thickeners. Information was insufficient to conclude which type of feed thickener is superior. Authors' conclusions: Gastro-oesophageal reflux is a physiological self resolving phenomenon in infants that does not necessarily require any treatment. However, we found moderate-certainty evidence that feed thickeners should be considered if regurgitation symptoms persist in term bottle-fed infants. The reduction of two episodes of regurgitation per day is likely to be of clinical significance to caregivers. Due to the limited information available, we were unable to assess the use of feed thickeners in infants who are breastfeeding or preterm nor could we conclude which type of feed thickener is superior.
  • Article
    Aim: In 2004 wide variation in the investigation and management of gastro-oesophageal reflux (GOR) of infants on UK major neonatal units was demonstrated. Our aim was to re-survey neonatal practitioners to determine current practice and whether it was now evidence based. Methods: A questionnaire was sent to all 207 UK neonatal units. Results: Responses were obtained from 84% of units. The most frequent "investigation" was a trial of therapy (83% of units); pH studies were used in 38%, upper GI contrast studies in 19% and multichannel intraluminal impedance (MII)/pH studies in 5%. Only six units suggested a threshold for an abnormal pH study and two units for an abnormal MII study. Infants were commenced on anti-reflux medication without investigation always in 32% of units, often in 29%, occasionally in 19% and only never in 1%. Gaviscon was used as first line treatment in 60% of units, other medications included ranitidine in 53%, thickening agents in 27%, proton pump inhibitors in 23%, domperidone in 22% and erythromycin in 6%. Conclusion: There remains a wide variation in diagnostic and treatment strategies for infants with suspected GOR on neonatal intensive care units, emphasizing the need for randomised trials to determine appropriate GOR management. This article is protected by copyright. All rights reserved.
Literature Review
  • Article
    The occurrence of gastroesophageal reflux after meals may be related to an increase in the rate of transient lower esophageal sphincter (LES) relaxations, the mechanisms of which are not understood. We investigated the effects of gastric distention on LES pressure in 16 normal subjects and 17 patients with gastroesophageal reflux disease. Intraluminal pressure was measured in the gastric fundus, LES, and esophageal body with a manometric catheter incorporating a sleeve device. Gastric distention was performed by injecting 0, 250, 500, or 750 ml of air in randomized order into a balloon and maintaining each stimulus for 15 min. Gastric distention did not significantly alter resting LES pressure in either group. During the basal period the rate of transient LES relaxation in the reflux patients (1.1 ± 0.4 per 15 min) was greater than that in the normal subjects (0.6 ± 0.1 per 15 min). Gastric distention resulted in a significant threefold to fourfold increase in the rate of transient LES relaxations in both groups. The reflux patients had a significantly greater proportion of complete relaxations (87%) than did the normal subjects (73%). We conclude that gastric distention, by significantly increasing the rate of transient LES relaxations in both normal subjects and patients with gastroesophageal reflux disease, may contribute to the postprandial increase in gastroesophageal reflux.
  • Article
    Objective: This study defined the clearance mechanisms of naturally occurring reflux episodes in normal subjects and patients with gastroesophageal reflux disease. Summary Background: Previous studies on acid clearance have been performed in the laboratory setting in supine subjects using acid instillation and stationary motility. The mechanisms of clearance have not been studied using ambulatory pH and motility monitoring. Methods: A new system capable of monitoring simultaneously for 24 hours pharyngeal pressure, esophageal motility, and pH was used to study the clearance of naturally occurring reflux episodes in 10 normal subjects and 18 patients with gastroesophageal reflux disease. Esophageal contraction waves were classified as primary (i.e., initiated by a pharyngeal swallow) and secondary (i.e., unrelated to a pharyngeal swallow). Results: A total of 1288 reflux episodes were analyzed, during which 2781 contraction waves occurred. Clearance (i.e., restoration of pH to > 4) occurred after primary peristalsis in 83% of reflux episodes. An additional 11% were cleared by pharyngeal swallows without an esophageal body response. Secondary waves were rare and when they occurred, only 19% were peristaltic. Secondary peristalsis cleared only 9 of the 1288 reflux episodes. Patients and normal subjects cleared reflux episodes similarly. Baseline swallowing frequency was 0.87/min during the daytime and increased to 2.59/min (p < 0.01) during daytime reflux episodes. Swallowing frequency in response to nighttime reflux episodes was less (1.42/min; p < 0.05). Conclusions: Pharyngeal swallowing is the most important mechanism for esophageal acid clearance. Secondary waves are rare, usually disorganized, and unimportant in clearing a reflux episode. During sleep, the mechanisms of clearance are depressed.
  • Article
    OBJECTIVE: Both transient lower esophageal sphincter (LES) relaxations (TLESRs) and periods of low/absent LES pressure (LESP) are the main mechanisms of gastroesophageal reflux. These events are believed to be triggered by stimuli from different areas of the upper GI tract. We aimed at investigating the relationship between LESP profile and gastric emptying and distension after meals of different composition in 30 children with gastroesophageal reflux disease (median age 7.0 yr, range 12 months–12 yr). METHODS: Recordings of LESP and intraesophageal pH for 1 h fasting and for 2 postprandial h were performed with a perfused sleeve catheter and flexible electrode, respectively; gastric emptying and distension of antral area were simultaneously recorded with real-time ultrasonography. Ten patients had a standard meal (group A), 10 had a high-volume meal (group B), and 10 had a high-volume and osmolality meal (group C). RESULTS: Postprandial esophageal acid exposure was significantly higher in patients of groups B and C than in patients of group A (p < 0.01); it was also more prolonged in patients of group C than in subjects of group B (p < 0.05). A higher postfeeding rate of reflux episodes caused by TLESRs was detected in patients of groups B and C as compared with patients of group A (p < 0.01). This increase did not statistically differ in patients of groups B and C. Patients of group C exhibited a higher postprandial rate of reflux episodes associated with low/absent tone of the LES as well as a more prolonged gastric emptying time and a higher postfeeding gastric distension as compared with patients of groups A and B (p < 0.01). Finally, a significant correlation was only found between the postprandial rate of reflux events resulting from low/absent LESP and the degree of antral distension in patients of group C (p < 0.01). CONCLUSION: Gastroesophageal reflux is worsened by increasing the volume and osmolality of meals through significant changes of LESP. Meals of high volume and meals with high volume and osmolality cause a comparable increase of reflux episodes as a result of TLESRs. However, meals with high volume and osmolality cause the higher degrees of esophageal acid exposure than meals with high volume resulting from a higher rate of reflux episodes associated with low/absent LESP. This finding correlates with a high postfeeding antral distension.
  • Article
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    Recent comprehensive guidelines developed by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition define the common entities of gastroesophageal reflux (GER) as the physiologic passage of gastric contents into the esophagus and gastroesophageal reflux disease (GERD) as reflux associated with troublesome symptoms or complications. The ability to distinguish between GER and GERD is increasingly important to implement best practices in the management of acid reflux in patients across all pediatric age groups, as children with GERD may benefit from further evaluation and treatment, whereas conservative recommendations are the only indicated therapy in those with uncomplicated physiologic reflux. This clinical report endorses the rigorously developed, well-referenced North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines and likewise emphasizes important concepts for the general pediatrician. A key issue is distinguishing between clinical manifestations of GER and GERD in term infants, children, and adolescents to identify patients who can be managed with conservative treatment by the pediatrician and to refer patients who require consultation with the gastroenterologist. Accordingly, the evidence basis presented by the guidelines for diagnostic approaches as well as treatments is discussed. Lifestyle changes are emphasized as first-line therapy in both GER and GERD, whereas medications are explicitly indicated only for patients with GERD. Surgical therapies are reserved for children with intractable symptoms or who are at risk for life-threatening complications of GERD. Recent black box warnings from the US Food and Drug Administration are discussed, and caution is underlined when using promoters of gastric emptying and motility. Finally, attention is paid to increasing evidence of inappropriate prescriptions for proton pump inhibitors in the pediatric population.
  • Article
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    Background: Inhibitors of gastric acid (IGA) are used for upper gastrointestinal bleeding or gastroesophageal reflux in preterm infants. The resultant increase in gastric pH may enhance the growth of pathogens and increase the risk of necrotizing enterocolitis (NEC). Our systematic review examined the association between IGA and NEC in preterm infants. Methods: Standard methodology of systematic reviews was followed. PubMed, Embase, Cochrane, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were searched in August 2012. Results: One case-control and one prospective cohort study (n = 11,346), both evaluating H2-blockers as IGA, were included. Meta-analysis showed a significant association between NEC and IGA (odds ratio [OR]: 1.78, 95% confidence interval [CI]: 1.4, 2.27, p < 0.00001). The prospective cohort study found higher incidence of infection (sepsis, pneumonia, urinary tract infection) with IGA (37.4% versus 9.8%, OR: 5.5, 95% CI: 2.9 to 10.4, p < 0.001). Conclusions: Exposure to H2 receptor antagonists may be associated with increased risk of NEC and infections in preterm infants.
  • Objective: To study the relationship between pepsinogen/pepsin in a mouth swab and clinical gastroesophageal reflux (GER) in preterm infants. Methods: Preterm infants [birth weight (BW) ≤ 2000 grams] on full enteral feeds were enrolled. Mouth swabs from cheek and below the tongue were collected 1, 2 and 3 hours after feeding. An enzymatic assay with substrate FITC-casein was used to detect pepsin A and C activity with further confirmation by Western blot. Blinded investigators reviewed the infant's medical record to clinically diagnose GER. Results: A total of 101 premature infants were enrolled. Pepsinogen/pepsin was detected in 45/101 (44.5%) infants in at least one sample. A clinical diagnosis of GER was made in 36/101 (35.6%) infants. Mouth swabs were positive in 26/36 (72%) infants with clinical GER and only 19/65 (29%) infants without GER (P<0.001). Similarly, the levels of pepsinogen/pepsin A and C were higher in the mouth swabs of infants with clinical GER. Conclusion: The detection of pepsinogen/pepsin in a mouth swab correlates with clinical GER in premature infants.