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Acta Pædiatrica ISSN 0803–5253
REGULAR ARTICLE
Transpyloric feeding in gastroesophageal-reflux–associated apnea
in premature infants
Sudipta Misra (smisra@pol.net)1, Kamlesh Macwan2, Viola Albert2
1.Divisions of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Illinois College of Medicine at Peoria and Children’s Hospital
of Illinois at OSF St. Francis Hospital, Peoria, Illinois, USA
2.Division of Neonatology, Department of Pediatrics, University of Illinois College of Medicine at Peoria and Children’s Hospital of Illinois at OSF St. Francis Hospital, Peoria,
Illinois, USA
Keywords
Apnea of prematurity, Gastroesophageal reflux,
Transpyloric feeding, Tube feeding
Correspondence
Sudipta Misra, Children’s Medical Center, MCG,
1446 Harper Street, Augusta, GA 30913, USA.
Tel.: (706) 721 4724 |Fa x: (706) 721 3791 |
Email: smisra@pol.net
Received
14 February 2007; revised 30 April 2007; accepted
27 June 2007.
DOI:10.1111/j.1651-2227.2007.00442.x
Abstract
Objective: The aetiological role of gastroesophageal reflux in apnea of prematurity is controversial. We
hypothesized that transpyloric feeds, which decreases reflux and aspiration, will not be associated
with decrease in reflux-related apnea.
Study design: The shows retrospective chart review of 41 premature babies on transpyloric feeds.
Fifteen infants meeting the inclusion criteria of apnea of prematurity and clinical evidence of
gastroesophageal reflux were included. Primary data points were number of apneas before and after
transpyloric feeds. t-statistics was used for analysis.
Results: Twelve of the 15 babies showed significant improvement on transpyloric feeds (p <. 005).
The nonresponders were identified within 48 h. After discontinuation of transpyloric feeds, 2
responders underwent antireflux surgery and 9 were discharged without further intervention. No
transpyloric-tube–related complication was documented.
Conclusion: Transpyloric feeds may be useful for diagnosis and management of suspected
gastroesophageal-reflux–associated apnea in a selected group of infants.
INTRODUCTION
Apnea is a common problem in premature newborns (1).
Gastroesophageal reflux is often implicated as one of the
aetiological factors. Empirical antireflux therapy is com-
mon in many neonatal intensive care units. Invasive diag-
nostic tests, such as long-term pH probe studies, are often
ordered to diagnose reflux. However, both apnea and re-
flux are common in premature newborns. A definite cause
and effect relationship between apnea and reflux has not
been established. Initial studies suggested gastroesophageal
reflux as an aetiological factor (2–4). However, that claim
has been disputed (5,6). Limitations of diagnostic tests for
reflux as well as its sporadic nature further complicate the
issue.
Small-bowel feeding has been shown to cause less gastroe-
sophageal reflux by radiolabel formula infusion study (7). We
hypothesized that if apnea is caused by gastroesophageal re-
flux then transpyloric feeds will not be associated with a
significant reduction of number of apneas.
METHODS
In this retrospective observational study, we reviewed the
records of premature newborns on transpyloric feeds be-
tween July 2000 and June 2004 at the neonatal intensive
care unit of the Children’s Hospital of Illinois at OSF St
Francis Hospital at Peoria, Illinois. In our newborn unit,
transpyloric feed is commonly used in suspected reflux-
associated apnea per protocol (see Fig. S1). Inclusion cri-
teria for this study were: (i) Newborns meeting the criteria
of apnea of prematurity as documented in the ‘apnea sheet.’
Apnea of prematurity was defined as sudden cessation of
breathing that lasted for at least 20 sec or was accompanied
by bradycardia or oxygen desaturation (cyanosis) in an in-
fant younger than 37 weeks gestational age (8). (ii) Common
causes of apnea, such as infection, metabolic abnormalities,
hypo or hyperthermia, hypoxia, anaemia, arrhythmias, and
medications, such as prostaglandin, upper airway malfor-
mations, sepsis, intracranial bleed, necrotizing enterocolitis,
etc, were excluded as aetiology. (iii) Clinical evidence of gas-
troesophageal reflux, such as significant vomiting, regurgita-
tion, and/or esophageal symptoms, such as arching back,
feeding difficulty, irritability, etc. (iv) Ineffective therapeutic
trials with caffeine.
Eight Fr Kendall Argyle IndwellTM (Tyco Healthcare
Group LP, Mansfield, MA) polyurethane nonweighed feed-
ing tubes were used. These were placed like nasogastric tubes
with 8–10 cm of excess length. The infant was placed in a
45◦angle on the right side to facilitate passage of the tube in
the duodenum. Transpyloric position of the tip of the tube
was confirmed by abdominal X-ray before starting continu-
ous feed with a pump. Numbers of apneas in 48 h before and
after transpyloric feeds were recorded. Thus the mean num-
ber of apneas/day was calculated in each infant. Readiness
for oral feeding was assessed in each infant per protocol.
However, the decision to discontinue transpyloric feedings
was made by the attending neonatologists according to clin-
ical condition and readiness of the baby to feed. Descriptive
and t-statistics were used for analysis. A p-value of less than
0.05 was taken to be statistically significant. The Institutional
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Misra et al. Gastroesophageal reflux and apnea in premature infants
Table 1 Reason for transpyloric feed in newborns (n =41)
Apnea 21
Desaturation only 18
Vomiting/aspiration 1
Unknown 1
Review Board of the UIC College of Medicine at Peoria ap-
proved this study.
RESULTS
Forty-one newborns were put on transpyloric feeding be-
tween December 2001 and June 2004. Though 21 infants
were started on transpyloric feeds for apnea (Table 1), on
review of the ‘apnea sheet’ only 15 met the criteria for apnea
of prematurity (8).
The mean gestational age and birth weight of these 15
infants were 27.6 ±2.9 weeks (range 24–36.3 weeks) and
1083.1 ±371.2 g (range 680–2190 g), respectively. Eleven
of these infants were below 28 weeks of gestation at birth.
Comorbid conditions included sepsis, chronic lung disease,
intraventricular haemorrhage, etc (Table 2). These comor-
bid conditions were passive or stable at the time of start-
ing transpyloric feeds and could not account for the apnea.
Before initiation of transpyloric feeds, 9 infants were on
combinations of ranitidine and metoclopramide; one each
received only ranitidine and metoclopramide. Two infants
received additional oral omeprazole. On transpyloric feeds,
there was no significant difference in the number of apneas
among 6 infants who were on antacids and/or prokinetics
and 7 who were not. Transpyloric feeding was initiated at
a mean chronological age of 32.25 ±9.34 days (range 20–
51 days) and continued for an average of 16.9 ±14.5 days
(range 2–48 days, median 10 days).
0
1
2
3
4
5
6
7
8
9
1 2
Bef or e and af t e r ND f ee ds
Responders = Continuous Lines
Non-Responders = Broken Lines
Figure 1 Mean number of apneas before and after transpyloric feeds (apnea/24 h, n =15). Responders =continuous lines; nonresponders =broken lines.
Table 2 Co-morbid conditions in newborns with apnea (n =15)
Extreme prematurity 11
Sepsis 7
Chronic lung disease 8
Intraventricular haemorrhage 2
Necrotizing enterocolitis 2
Others 12
Includes multiple diagnoses in individual subjects.
On transpyloric feeds, 12 infants had documented reduc-
tion of apneas. The mean number of apneas in the whole
group decreased from 2.43/days (range 1–8, median 2) to
1.06/days (range 0–3, median 1; p <0.05 by paired t-test).
Three infants did not respond to transpyloric feeds, 2 had
no change in numbers of apneas whereas 1 had more ap-
neic spells (Fig. 1). Four infants had less than two doc-
umented apneic episodes per day for 3 consecutive days
before transpyloric feeds were initiated. Apneic episodes
improved in two (50%) of them on transpyloric feeds. Vom-
iting and/or regurgitation resolved in all babies on transpy-
loric feeding. Review of medical records of all 41 infants did
not reveal complications, such as intestinal perforation, peri-
tonitis, gastrointestinal haemorrhage, migration of the tube
to the abdominal or thoracic cavity, etc, that could be related
to transpyloric tube feeding.
Among the 12 newborns that responded to transpyloric
feeding, 2 underwent antireflux surgery, one due to recur-
rence of symptoms after discontinuation of transpyloric feed
and the other along with a gastrostomy tube placement for
poor feeding. One baby was transferred to another facil-
ity while on transpyloric feeds and was lost to follow-up.
The remaining newborns were discharged home on oral
feeds.
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Gastroesophageal reflux and apnea in premature infants Misra et al.
DISCUSSION
The role of gastroesophageal reflux in apnea of prematurity
is controversial. Co-existence and possible aetiological re-
lationship between gastroesophageal reflux and apnea have
been widely reported(2–4). Recent studies in a small number
of infants using sophisticated techniques have failed to con-
firm an aetiological role of gastroesophageal reflux in apnea
of prematurity (5,6). However, such studies are complicated
by unreliable diagnostic techniques, day-to-day variability of
reflux and lack of studies with appropriate sample size and
power (9,10). Upper gastrointestinal barium X-ray is not rec-
ommended as a diagnostic test for gastroesophageal reflux
(11), and pH probe studies are limited by acid-neutralizing
capability of most formulas and inability to detect non-acid
refluxes that can cause aspiration (9). In fact, clinical indi-
cators, such as vomiting, arching back, coughing, etc, may
be more useful for a presumptive diagnosis of reflux in pre-
mature infants than invasive tests.
In this case series, we have explored a simple logical ther-
apeutic approach to evaluate the causal effect of gastroe-
sophageal reflux on apnea. In our institution transpyloric
feed is being used as an empirical therapy for apnea and
desaturation suspected to be due to gastroesophageal re-
flux (see Fig. S1). We have discontinued using invasive tests
to document gastroesophageal reflux as these are of doubt-
ful value and mere co-existence of two conditions does not
prove their aetiological role. For the purpose of this study,
we included only those with clearly documented apnea in
the neonatal records. Usual causes of apnea were excluded
in these infants. They did not respond to usual therapeutic
measures to control apnea. These babies had clinical indica-
tors of reflux and most of these babies had failed ‘standard’
pharmacotherapy to control gastroesophageal reflux.
Four babies had less than two apneic episodes/day for
3 consecutive days. Use of strict inclusion criteria for ap-
nea might have excluded episodes that were of clinical con-
cern in these babies but did not meet the criteria. Though
the possibility that these apneic episodes were due to day-
to-day variation of respiratory pattern cannot be ruled out,
they were persistent, recurring and were nonresponsive to
usual therapy. Half of these babies responded to transpy-
loric feeding. Transpyloric feeding has been extensively used
in newborns for enteral feeding (12). It is less likely to cause
gastroesophageal reflux (7). Transpyloric feeding has been
shown to significantly decrease the incidence of aspiration
when compared to intragastric feeds (13). So, if the apnea
was related to gastroesophageal reflux, transpyloric feed-
ing should result in significant improvement. Those without
reflux-related apnea would not benefit from this interven-
tion. In our study, responders were distinguished from non-
responders within 48 h of starting transpyloric feeds (Fig. 1).
The decrease in the number of apneas after starting transpy-
loric feeds was statistically significant. Nine of the 12 babies
did not have recurrence of apnea after discontinuation of
transpyloric feeds. Age-related maturity of gastrointestinal
function and improved nutrition may account for nonrecur-
rence of apnea after discontinuation of transpyloric feeds
(1,14).
Concerns have been expressed about transpyloric-tube–
related complications in newborns (12). However, no per-
foration with or without complication was reported in this
meta-analysis. Authors acknowledged that the increased in-
cidence of ‘gastrointestinal symptoms’ and mortality might
have been caused by one large study with possible assign-
ment bias. We routinely use small-calibre soft polyurethane
nonweighed feeding tubes. No such complications were en-
countered in our entire patient population (n =41) as well in
other areas of Children’s Hospital where this form of feeding
is used frequently.
This is an uncontrolled empirical study in a small number
of subjects selected after multiple layers of clinical screening.
It explores a novel, common sense; inexpensive approach to
managing infants suspected of having apnea due to reflux
and avoids expensive invasive tests of doubtful value.
We conclude that continuous transpyloric feeding is a
safe and useful diagnostic and therapeutic option in a select
group of newborns with apnea of prematurity, suspected to
be due to gastroesophageal reflux. A prospective multicen-
tre study with appropriate power is warranted to explore this
simple inexpensive approach.
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Supplementary material
The following supplementary material is available for this
article:
Figure S1 Modified from Berman S. Neonatal apnea in pe-
diatric decision making. Berman S., editor, 1st ed. Philadel-
phia, PA: B. C. Decker, Inc., 1984: 52–3.
This material is available as part of the online article from:
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1651-
2227.2007.00442.x
(This link will take you to the article abstract).
Please note: Blackwell Publishing is not responsible for the
content or functionality of any supplementary materials sup-
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rial) should be directed to the corresponding author for the
article.
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