Alimentación Trasnpilorica Vs Gastrica en El Pretermino

Cochrane Database of Systematic Reviews
Transpyloric versus gastric tube feeding for preterm infants

(Review)
Watson J, McGuire W
Watson J, McGuire W.
Transpyloric versus gastric tube feeding for preterm infants.
Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No.: CD003487.
DOI: 10.1002/14651858.CD003487.pub3.
www.cochranelibrary.com
Transpyloric versus gastric tube feeding for preterm infants (Review)

Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Figure 4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Figure 5. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Figure 6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Analysis 1.1. Comparison 1 Transpyloric versus gastric tube feeding for preterm infants: growth, Outcome 1 Change in
weight (g/week). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
crown heel length (mm/week). . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
occipito-frontal head circumference (mm/week). . . . . . . . . . . . . . . . . . . . . . . 25
subscapular skinfold thickness (mm/week). . . . . . . . . . . . . . . . . . . . . . . . . 25
Analysis 2.1. Comparison 2 Transpyloric versus gastric tube feeding for preterm infants: adverse events, Outcome 1 Death
prior to hospital discharge. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Analysis 2.2. Comparison 2 Transpyloric versus gastric tube feeding for preterm infants: adverse events, Outcome 2 Death
prior to hospital discharge (excluding Laing 1986). . . . . . . . . . . . . . . . . . . . . . 27
Analysis 2.3. Comparison 2 Transpyloric versus gastric tube feeding for preterm infants: adverse events, Outcome 3
Gastrointestinal disturbance (including diarrhoea) prior to hospital discharge. . . . . . . . . . . . . 28
Gastrointestinal disturbance (including diarrhoea) prior to hospital discharge (excluding Laing 1986). . . . 29
Necrotising enterocolitis prior to hospital discharge. . . . . . . . . . . . . . . . . . . . . 30
Necrotising enterocolitis prior to hospital discharge (excluding Laing 1986). . . . . . . . . . . . . 31
Aspiration pneumonia prior to hospital discharge. . . . . . . . . . . . . . . . . . . . . . 32
Intestinal perforation prior to hospital discharge. . . . . . . . . . . . . . . . . . . . . . . 33
WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
Transpyloric versus gastric tube feeding for preterm infants (Review) i

[Intervention Review]
Julie Watson1 , William McGuire2

1 Maternal and Infant Health and Care, Yorkshire and the Humber Health Innovation and Education Cluster, Department of Health
Sciences, University of York, York, UK. 2 Hull York Medical School & Centre for Reviews and Dissemination, University of York, York,
UK
Contact address: William McGuire, Hull York Medical School & Centre for Reviews and Dissemination, University of York, York,
Y010 5DD, UK. William.McGuire@hyms.ac.uk.
Editorial group: Cochrane Neonatal Group.

Publication status and date: New search for studies and content updated (no change to conclusions), published in Issue 2, 2013.
Review content assessed as up-to-date: 30 June 2012.
Citation: Watson J, McGuire W. Transpyloric versus gastric tube feeding for preterm infants. Cochrane Database of Systematic Reviews
2013, Issue 2. Art. No.: CD003487. DOI: 10.1002/14651858.CD003487.pub3.
ABSTRACT
Background
Enteral feeding tubes for preterm infants may be placed in the stomach (gastric tube feeding) or in the upper small bowel (transpyloric
tube feeding). There are potential advantages and disadvantages to both routes.
Objectives
To determine the effect of feeding via the transpyloric route versus feeding via the gastric route on feeding tolerance, growth and
development, and adverse consequences (death, gastro-intestinal disturbance including necrotising enterocolitis, aspiration pneumonia,
chronic lung disease, pyloric stenosis) in preterm infants.
Search methods
We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central
Register of Controlled Trials (The Cochrane Library 2012, Issue 3), MEDLINE, EMBASE, and CINAHL (to June 2012), conference
proceedings, and previous reviews.
Selection criteria
Randomised or quasi-randomised controlled trials comparing transpyloric with gastric tube feeding in preterm infants.
Data collection and analysis
We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and
data extraction by two review authors. We synthesised data using a fixed-effect model and reported typical risk ratio (RR), risk difference
(RD), and mean difference (MD).
Main results
We found nine eligible trials in which a total of 359 preterm infants participated. All of the trials contained methodological weaknesses
with lack of allocation concealment, absence of blinding of caregivers or assessors, and incomplete follow-up being the major potential
sources of bias. The included trials did not detect any statistically significant effects on feeding tolerance or in-hospital growth rates.
Meta-analyses found that infants allocated to receive transpyloric feeding had a higher risk of gastro-intestinal disturbance (typical RR
1.48 (95% confidence interval (CI) 1.05 to 2.09); typical RD 0.09 (95% CI 0.02 to 0.17); number needed to treat for an additional
Transpyloric versus gastric tube feeding for preterm infants (Review) 1
harmful outcome (NNTH) 10 (95% CI 6 to 50); six studies, 245 infants) and all-case mortality (typical RR 2.46 (95% CI 1.36
to 4.46); typical RD 0.16 (95% CI 0.07 to 0.26); NNTH 6 (95% CI 4 to 14); six studies, 217 infants). However, the trial that
contributed most weight to these findings was likely to have been affected by selective allocation of the less mature and sicker infants
to transpyloric feeding. We did not find any statistically significant differences in the incidence of other adverse events, including
necrotising enterocolitis, intestinal perforation, and aspiration pneumonia.
Authors’ conclusions
The available data do not provide evidence of any beneficial effect of transpyloric feeding for preterm infants. Some evidence of
harm exists, including a higher risk of gastrointestinal disturbance and mortality, but these findings should be interpreted and applied
cautiously because of methodological weaknesses in the included trials.
PLAIN LANGUAGE SUMMARY
Preterm infants often have poor co-ordination of sucking and swallowing and this can delay the establishment of safe oral feeding.
Enteral feeds may be delivered through a catheter passed via the nose or the mouth into either the stomach (gastric feeding) or beyond
the stomach into the next part of the bowel (transpyloric feeding). This review of trials found that babies receiving transpyloric feeding
had more adverse events without any evidence of benefit over gastric feeding.
BACKGROUND Why it is important to do this review

Feeding by the transpyloric route also has potential problems.
The gastric phase of the digestion is by-passed and secretion of
upper intestinal hormones and growth factors may be impaired
Description of the condition (Milner 1981). There is also a risk that potentially pathogenic or-
Preterm infants have poor co-ordination of sucking and swallow- ganisms, which would have been removed in the acidic environ-
ing and this can delay the establishment of safe oral feeding. Enteral ment of the stomach, may be delivered directly into upper small
feeds may be delivered through a catheter passed via the nose or bowel (Dellagrammaticas 1983). These factors might contribute
the mouth into the stomach or upper small intestine. The gastro- to a higher risk of necrotising enterocolitis in infants fed via the
oesophageal valve is more lax and gastric peristalsis and emptying transpyloric route as suggested by observational studies (Vazquez
is less effective in preterm than in term infants (Berseth 1989). A 1980; Vinocur 1990). Additionally, transpyloric feeding tubes are
further concern with intragastric feeding for preterm infants is that difficult to position and, unlike gastric tubes, the position of the
lower oesophageal sphincter laxity results in gastro-oesophageal transpyloric catheter must be confirmed with imaging. Follow-
reflux (GOR) and, putatively, GOR-attributed apnoea or brady- ing placement, the transpyloric tube may still migrate back to the
cardia and aspiration pneumonia (Misra 2007; Malcolm 2009). stomach. Serious adverse events including cases of intestinal per-
foration and of pyloric stenosis have also been reported (Boros
1974; Raine 1982).
Description of the intervention

Placement of the enteral feeding tube in the duodenum or jejunum
(transpyloric feeding) rather than the stomach (gastric feeding) OBJECTIVES
ensures delivery of enteral feeds to the main sites of nutrient ab-
sorption and has the theoretical advantage of decreasing the po- To determine the effect of feeding via the transpyloric route ver-
tential for oesophageal reflux, reflux-associated apnoea or brady- sus feeding via the gastric route on feeding tolerance, growth and
cardia, and aspiration pneumonia. development, and adverse consequences (death, gastro-intestinal
disturbance including necrotising enterocolitis, aspiration pneu- iv) lethargy, hypotonia, or apnoea (or combination of
monia, chronic lung disease, pyloric stenosis) in preterm infants. these); or
v) a diagnosis confirmed at surgery or autopsy.
4. Aspiration pneumonia/pneumonitis: clinical or radiological
METHODS evidence of lower respiratory tract compromise that has been
attributed to covert or evident aspiration of gastric contents.
5. Intestinal perforation.
6. Pyloric stenosis requiring surgical intervention.
Criteria for considering studies for this review
7. Frequency of episodes of prolonged apnoea (no respiratory
effort > 20 seconds) or bradycardia (< 60 beats per minute), or
apnoea/bradycardia necessitating stimulation, oxygen
Types of studies
administration increase, or positive pressure ventilation.
Controlled trials using either random or quasi-random patient 8. Chronic lung disease defined as an additional oxygen
allocation. requirement at 36 weeks post menstrual age.
Types of participants
Search methods for identification of studies
Preterm infants who receive enteral tube feeding.
We used the standard search strategy of the Cochrane Neonatal
Review Group.
Types of interventions
Trials comparing transpyloric versus gastric tube feeding with
catheters passed via the nose or mouth. Trials of gastrostomy, duo- Electronic searches
denostomy, or jejunostomy feeding were not included. Trials in We searched the Cochrane Central Register of Controlled Tri-
which parenteral nutritional support was available during the pe- als (The Cochrane Library 2012, Issue 3), MEDLINE (1966 to
riod of advancement of enteral feeds were acceptable, provided June 2012), and EMBASE (1980 to June 2012). The search strat-
that the groups received similar treatment other than the route of egy used the following text words and Medical Subject Headings:
enteral feeding. [Infant-Newborn/, OR infan*, OR neonat*, OR prematur*, OR
preterm], AND [Infant-Nutrition/, OR Feeding-Methods/, OR
Intubation, Gastrointestinal/, OR gastric, OR transpyloric, OR
Types of outcome measures nasoduodenal, OR nasojejunal]. We used a search filter in MED-
LINE and EMBASE to limit retrieval to clinical trials. We did not
apply any language restrictions.
Primary: feed tolerance and growth
We searched ClinicalTrials.gov, Current Controlled Trials, and
1. Days from birth to establish full enteral tube feeds WHO Clinical Trials Registry for completed or ongoing trials.
independently of parenteral fluids or nutrition.
2. Growth: rates of change in weight, length, head
circumference, or skinfold thickness. Searching other resources
We examined the references in studies identified as potentially rel-
evant. We also searched the abstracts from the annual meetings
Secondary: adverse effects
of the Pediatric Academic Societies (1993 to 2012), the European
1. Death prior to hospital discharge. Society for Pediatric Research (1995 to 2011), the UK Royal Col-
2. Gastrointestinal disturbance such as diarrhoea or feeding lege of Paediatrics and Child Health (2000 to 2012), and the Peri-
intolerance that results in cessation of enteral feeding. natal Society of Australia and New Zealand (2000 to 2012). We
3. Necrotising enterocolitis confirmed by at least two of the considered trials reported only as abstracts to be eligible if suffi-
following features: cient information was available from the report, or from contact
i) abdominal radiograph showing pneumatosis with the authors, to fulfil the inclusion criteria.
intestinalis or gas in the portal venous system or free air in the
abdomen;
ii) abdominal distension with abdominal radiograph with
gaseous distension or frothy appearance of bowel lumen (or
Data collection and analysis
both); We used the standard methods of the Cochrane Neonatal Review
iii) blood in stool; Group.

Selection of studies iii) unclear.
Two review authors screened the title and abstract of all studies
identified by the above search strategy. We assessed the full text of
any potentially eligible reports and excluded those studies that did Measures of treatment effect
not meet all of the inclusion criteria. We discussed any disagree- We calculated risk ratio (RR) and risk difference (RD) for dichoto-
ments until consensus was achieved. mous data and mean difference (MD) for continuous data with re-
spective 95% confidence intervals (CI). We determined the num-
ber needed to treat for an additional beneficial outcome (NNTB)
Data extraction and management
or an additional harmful outcome (NNTH) for a statistically sig-
We used a data collection form to aid extraction of relevant infor- nificant RD.
mation from each included study. Two review authors extracted
the data separately. We discussed any disagreements until consen-
sus was achieved. We asked the investigators for further informa-
Unit of analysis issues
tion if data from the trial reports were insufficient.
The unit of analysis is the participating infant in individually ran-
domised trials and the neonatal unit for cluster-randomised trials.
Assessment of risk of bias in included studies
We used the criteria and standard methods of the Cochrane
Neonatal Review Group to assess the methodological quality of Dealing with missing data
any included trials. Additional information from the trial authors We requested missing study data from the trial investigators.
was requested to clarify methodology and results as necessary. We
evaluated and reported the following issues in the ’Risk of bias’
tables:
1. Sequence generation: We categorised the method used to Assessment of heterogeneity
generate the allocation sequence as: If more than one trial was included in a meta-analysis, we exam-
i) low risk: any random process e.g. random number ined the treatment effects of individual trials and heterogeneity
table; computer random number generator; between trial results by inspecting the forest plots. We calculated
ii) high risk: any non random process e.g. odd or even the I² statistic for each analysis to quantify inconsistency across
date of birth; patient case-record number; studies and describe the percentage of variability in effect estimates
iii) unclear. that may be due to heterogeneity rather than sampling error. If
2. Allocation concealment: We categorised the method used substantial (I² > 50%) heterogeneity was detected, we explored
to conceal the allocation sequence as: the possible causes (for example, differences in study design, par-
i) low risk: e.g. telephone or central randomisation; ticipants, interventions, or completeness of outcome assessments)
consecutively numbered sealed opaque envelopes; in sensitivity and subgroup analyses.
ii) high risk: open random allocation; unsealed or non-
opaque envelopes, alternation; date of birth;
iii) unclear. Assessment of reporting biases
3. Blinding: We assessed blinding of participants, clinicians
and caregivers, and outcome assessors separately for different If more than five trials were included in a meta-analysis, we con-
outcomes and categorised the methods as: ducted a funnel plot analysis.
i) low risk;
ii) high risk;
iii) unclear. Data synthesis
4. Incomplete outcome data: We described the completeness We used a fixed-effect model for meta-analyses.
of data including attrition and exclusions from the analysis for
each outcome and any reasons for attrition or exclusion where
reported. We assessed whether missing data were balanced across
groups or were related to outcomes. Where sufficient information Subgroup analysis and investigation of heterogeneity
was reported or supplied by the trial authors, we re-included We pre-specified subgroup analysis of trials of routine (non-selec-
missing data in the analyses. We categorised completeness as: tive) use of transpyloric feeding versus selective transpyloric feed-
i) low risk: < 20% missing data; ing for infants with confirmed or suspected GOR or GOR-at-
ii) high risk: > 20% missing data; tributed apnoea or bradycardia.

RESULTS Blinding
The caregivers or assessors were aware of the intervention to which
infants had been allocated in all of the included trials.
Description of studies
See: Characteristics of included studies; Characteristics of excluded
Incomplete outcome data
studies.
We found nine eligible trials (Van Caillie 1975; Wells 1975; In general, short-term outcome data assessment was complete.
Pyati 1976; Roy 1977; Drew 1979; Pereira 1981; Whitfield 1982; However, growth data were often not reported for infants who had
Laing 1986; Macdonald 1992; see table Characteristics of included failed to complete the study, for example because the enteral tube
studies). feeding method was changed (that is, not an intention-to-treat
analysis). For adverse outcomes, reporting was generally complete
or available indirectly from the text of the report.
Included studies
All of the included studies were undertaken in the 1970s or early
1980s. Most recruited very low birth weight infants (birth weight Effects of interventions
< 1500 g). However, only infants grown appropriately for ges-
tational age were eligible for inclusion in most of the trials. In
some trials infants who required respiratory or ventilatory support
were not eligible for inclusion. Feeding by the allocated route was Primary outcomes: feed tolerance and growth
usually started within the first few days after birth when enteral
feeds were commenced. Feeding tubes used were made of silastic,
polyvinyl, or polypropylene. The transpyloric tubes were placed 1. Days from birth to establish full enteral tube feeds
in the second or third part of duodenum or the jejunum with independently of parenteral fluids or nutrition
the assistance of positioning of the infant and peristalsis. In all of This outcome was reported by Macdonald 1992 and by Pereira
the trials the position of the tube was confirmed radiologically. 1981. These investigators did not find any statistically significant
All trials reported nutrient (usually energy) intake and short-term differences but the data were presented without standard devia-
growth as the primary outcomes. In most reports, data on adverse tions and could not be used in a meta-analysis.
events (including death, necrotising enterocolitis, intestinal per-
foration, and aspiration pneumonia) were available.
2. Growth
Excluded studies All of the included trials reported short-term (prior to discharge
from hospital) growth outcomes. One study provided data on
Ten reports were excluded following inspection of the full report longer-term (following discharge from hospital) growth (Whitfield
(Cheek 1973; Valman 1973; Boros 1974; Chen 1974; Uauy 1975; 1982).
Wolfsdorf 1975; Avery 1977; Celestin 1978; Price 1978; Agarwal
1980; see table Characteristics of excluded studies).
a. Short-term weight gain (Outcome 1.1)
Seven trials reported no statistically significant differences in the
Risk of bias in included studies rate of weight gain (Pyati 1976; Roy 1977; Drew 1979; Whitfield
All of the trials were small (total N = 359) and none presented a 1982; Laing 1986; Macdonald 1992). Two trials found statistically
power or sample size calculation. significantly higher rates of weight gain in the group allocated to
transpyloric feeding (Van Caillie 1975; Wells 1975). Four trials
provided data in a form that could be used in a meta-analysis (Roy
Allocation 1977; Van Caillie 1975; Whitfield 1982; Macdonald 1992). The
In most of the trials, allocation was not concealed and the assign- combined data from these studies did not reveal a statistically sig-
ment of infants to one or other feeding route could have been nificant difference: mean difference (MD) -0.5 (95% confidence
predicted. interval (CI) -27 to 16) g/week (Figure 1).

Figure 1. Forest plot of comparison: 1 Transpyloric versus gastric tube feeding for preterm infants: Growth,
outcome: 1.1 Change in weight (g/week).
b. Short-term linear growth (Outcome 1.2)

In the five trials that reported linear growth, the investigators did
not find any statistically significant difference in the rate of increase
in crown heel length (Roy 1977; Drew 1979; Pereira 1981; Laing
1986; Macdonald 1992). Only three studies provided data in a
form that could be used in a meta-analysis (Roy 1977; Laing 1986;
Macdonald 1992). The combined data from these studies did not
reveal a statistically significant difference: MD -0.7 (95% CI -2.4
to 1.0) mm/week (Figure 2).
Figure 2. Forest plot of comparison: 2 Transpyloric versus gastric tube feeding for preterm infants: Adverse
events, outcome: 2.1 Death prior to hospital discharge.
MD 0.6 (95% CI -0.9 to 2.1) mm/week.

c. Short-term head growth (Outcome 1.3)
In the five trials that reported head growth, the investigators did
not find any statistically significant difference in the rate of increase
in occipito-frontal head circumference (Roy 1977; Drew 1979; d. Short-term change skinfold thickness (Outcome 1.4)
Pereira 1981; Laing 1986; Macdonald 1992). Only two reports
provided data in a form that could be used in a meta-analysis This was reported in one study (Roy 1977). The investigators did
(Laing 1986; Macdonald 1992). The combined data from these not find a statistically significant difference: MD -0.2 (95% CI -
studies did not demonstrate a statistically significant difference: 1.2 to 0.8) mm/week.
e. Longer-term growth measures. Although there was often incomplete follow-up of re-
Growth following hospital discharge was reported in only one of cruited infants with regard to growth data, in the majority of the
the trials (Whitfield 1982). At the expected date of delivery, body reports we have been able to determine the incidence of adverse
weight and occipito-frontal head circumference were statistically events for the complete or near complete cohort.
significantly lower in the nasojejunal group: MD -0.3 (95% CI -
0.6 to -0.03) kg, and -1.0 (95% CI -1.7 to -0.3) cm, respectively. At
three and six months after the expected date of delivery, there were 1. Death before discharge from hospital (Outcome 2.1)
no statistically significant differences between the groups in body Six trials reported this outcome (Wells 1975; Van Caillie 1975;
weight or occipito-frontal head circumference. However, there was Drew 1979; Whitfield 1982; Laing 1986; Macdonald 1992). Only
considerable loss to follow-up, mainly in the transpyloric feeding Laing 1986 found that nasojejunal feeding was associated with
group where 12 of the recruited 28 infants were not assessed at six a statistically significantly higher mortality rate. The other trials
months. did not find any statistically significant difference. Meta-analysis
found a statistically significantly higher rate of death in the infants
who were fed via the transpyloric route: typical risk ratio (RR) 2.5
Secondary outcomes: adverse effects (95% CI 1.4 to 4.5); typical risk difference (RD) 0.16 (95% CI
Seven of the trials reported adverse events including death, necro- 0.07 to 0.26); number needed to treat for an additional harmful
tising enterocolitis, gastrointestinal disturbance, aspiration pneu- outcome (NNTH) 6 (95% CI 4 to 14) (Figure 2). There was not
monia, and intestinal perforation. Adverse events were often re- any evidence of heterogeneity (I² = 0%) or funnel plot asymmetry
ported as withdrawal criteria rather than as pre-defined outcome (Figure 3).
Figure 3. Funnel plot of comparison: 2 Transpyloric versus gastric tube feeding for preterm infants: Adverse
events, outcome: 2.1 Death prior to hospital discharge.

In a sensitivity analysis (Outcome 2.2), Laing 1986 was excluded
because of the differences in the baseline characteristics of the feed- 1977; Drew 1979; Pereira 1981; Whitfield 1982; Laing 1986;
ing groups. When only the remaining five studies were included Macdonald 1992). None of the individual trials found any sta-
in the meta-analysis, the difference was not statistically significant: tistically significant difference in the incidence of gastrointesti-
typical RR 2.2 (95% CI 0.9 to 5.4); typical RD 0.1 (95% CI 0.00 nal disturbance. Meta-analysis found a statistically significantly
to 0.2). higher risk of gastrointestinal disturbance in the infants fed via
the transpyloric route: typical RR 1.48 (95% CI 1.05 to 2.09);
typical RD 0.09 (95% CI 0.02 to 0.17); NNTH 10 (95% CI 6
2. Gastrointestinal disturbance such as diarrhoea or feeding to 50) (Figure 4). There was not any evidence of heterogeneity (I²
intolerance (Outcome 2.3) = 0%) but funnel plot inspection suggested asymmetry and over-
Seven trials reported this outcome (Van Caillie 1975; Roy representation of smaller trials with large effect sizes (Figure 5).
Figure 4. Forest plot of comparison: 2 Transpyloric versus gastric tube feeding for preterm infants: Adverse
events, outcome: 2.3 Gastrointestinal disturbance (including diarrhoea) prior to hospital discharge.

Figure 5. Funnel plot of comparison: 2 Transpyloric versus gastric tube feeding for preterm infants: Adverse
events, outcome: 2.3 Gastrointestinal disturbance (including diarrhoea) prior to hospital discharge.
In a sensitivity analysis (Outcome 2.4), removing Laing 1986,

there remained a statistically significant difference in the incidence vidual trials, nor a meta-analysis of the studies, found any statisti-
of gastrointestinal disturbance: typical RR 1.4 (95% CI 1.02 to cally significant difference in the incidence of aspiration pneumo-
2.0); typical RD 0.1 (95% CI 0.01 to 0.21); NNTH 10 (95% CI nia/pneumonitis. Meta-analysis: typical RR 1.35 (95% CI 0.44
5 to 100). to 4.14); typical RD 0.02 (95% CI -0.06 to 0.1).
3. Necrotising enterocolitis (Outcome 2.5) 5. Intestinal perforation (Outcome 2.8)

Seven trials (Van Caillie 1975; Wells 1975; Drew 1979; Pereira Four trials (Van Caillie 1975; Roy 1977; Pereira 1981; Whitfield
1981; Whitfield 1982; Laing 1986; Macdonald 1992 ) reported 1982) reported this outcome. Of the 129 infants studied, there
this outcome. None of the individual trials, nor a meta-analysis was only one reported case of intestinal perforation. None of the
of the studies, found any statistically significant difference in the individual trials, nor a meta-analysis of the studies, found any
incidence of necrotising enterocolitis: typical RR 0.6 (95% CI 0.3 statistically significant difference in the incidence of aspiration
to 1.5); typical RD -0.03 (95% CI -0.09 to 0.03). pneumonia. Meta-analysis: typical RR 2.3 (95% CI 0.1 to 50.1);
In a sensitivity analysis (Outcome 2.6), removing Laing 1986, typical RD: 0.01 (95% CI -0.05 to 0.08).
there was not any statistically significant difference in the incidence
of necrotising enterocolitis: typical RR 0.9 (95% CI 0.3 to 2.6);
typical RD -0.01 (95% CI -0.08 to 0.06). 6. Pyloric stenosis
This outcome was not reported in any of the trials.
4. Aspiration pneumonia/pneumonitis (Outcome 2.7)

Four trials (Van Caillie 1975; Pyati 1976; Drew 1979; Pereira 7. Frequency of apnoea/bradycardia
1981; Macdonald 1992) reported this outcome. None of the indi- This outcome was not reported in any of the trials.

8. Chronic lung disease Summary of main results
This outcome was not reported in any of the trials. We did not find any evidence of benefit of transpyloric compared
with gastric feeding in preterm infants. We found some evidence
that transpyloric feeding increases the risk of gastrointestinal dis-
turbance and mortality. However, many of the studies included in
the review had a variety of methodological weaknesses and these
findings need to be interpreted and applied with caution (Figure
DISCUSSION 6).
Figure 6. ’Risk of bias’ graph: review authors’ judgements about each risk of bias item presented as
percentages across all included studies.
Overall completeness and applicability of reduce the frequency or degree of GOR and GOR-related apnoea/
evidence bradycardia and prevent pulmonary aspiration of intestinal con-
Only two of the included trials assessed the effect of transpyloric tents (Misra 2007; Malcolm 2009). This review did not find any
versus gastric tube feeding on measures of ’feed tolerance’ such as evidence that transpyloric feeding affected the risk of aspiration
the time taken to establish enteral feeding. With regard to growth pneumonia but a modest yet important effect size has not been ex-
parameters, in many of the trials the growth data from infants who cluded. However, none of the included trials assessed the effect of
developed complications during the study period, or in whom transpyloric versus gastric tube feeding on the incidence of GOR-
enteral tube placement was unsuccessful, were not reported. In the related apnoea/bradycardia, and none of the trials specifically re-
largest included trial only 41 of the 80 infants who entered the cruited infants with confirmed or suspected GOR or GOR-at-
study were included in the growth data analysis (Laing 1986). In tributed problems. Although uncertainty exists as to whether GOR
Drew 1979, of the 66 infants allocated to a feeding route, there is an important cause of apnoea/bradycardia in preterm infants
were outcome data for only 44 infants. Given these levels of loss (Peter 2002; Di Fiore 2005; Corvaglia 2009), it has been proposed
to follow-up, the findings should be regarded with caution. For that clinical trials are warranted to evaluate whether transpyloric
example, it may be that the repeated failed attempts to position feeding is an effective prevention or treatment option in preterm
the transpyloric tube introduces a delay in starting or establishing infants with clinical problems attributed to GOR (Misra 2007;
nutritional input. Since it is plausible that such delay may affect Malcolm 2009).
growth, the findings may have been different in a true intention-
to-treat analysis.
Gastro-oesophageal reflux (GOR), aspiration, and Quality of the evidence
apnoea/bradycardia
The finding that transpyloric feeding increased the risk of mortal-
Observational studies have suggested that transpyloric feeding may ity should also be interpreted carefully since it is possible that the
pooled estimate in the meta-analysis is over-inflated by allocation Implications for practice
bias in several of the trials. In particular, the outcomes for Laing
The available trial data do not provide evidence that transpyloric
1986 (which contributes > 50% of the weight to the pooled risk
feeding has benefits for preterm infants but do raise concerns about
ratio) may have been affected by preferential allocation of less ma-
a higher risk of adverse affects including gastrointestinal distur-
ture or sicker infants to the transpyloric feeding group. When this
bance and mortality. However, these findings need to be inter-
study was excluded from the meta-analysis the increase in mortal-
preted and applied cautiously because of methodological weak-
ity in the transpyloric group was not statistically significant.
nesses in the included trials.
Similarly, the increase in the risk of gastrointestinal disturbance in
infants who received transpyloric feeding may have been inflated
Implications for research
by allocation bias as well as by ascertainment or surveillance biases
since caregivers and clinicians were aware of the allocated inter- Even if the concerns regarding an effect on mortality are dis-
vention in all of the trials. We did not detect any statistically sig- counted, the lack of evidence of an effect on growth and the find-
nificant differences in the incidences of necrotising enterocolitis ing of an higher risk of gastrointestinal disturbance suggest that
or intestinal perforation between the feeding groups. Additionally, a randomised controlled trial of routine transpyloric versus gas-
although it may be pragmatic to compare continuous transpyloric tric tube feeding in preterm infants is not a priority. The lack of
feeding with intermittent or bolus gastric feeding, as was the case trial data on the effect of transpyloric feeding on preventing or
in seven of the included trials, this co-intervention may also have treating gastro-oesophageal reflux-attributed apnoea/bradycardia
affected the outcomes. The Cochrane review that compared con- means that a randomised controlled trial in this select population
tinuous nasogastric tube feeding versus intermittent bolus feeding may be considered appropriate by clinicians and families.
for preterm infants concluded that the clinical benefits and harms
could not be reliably discerned from the available data from ran-
domised trials (Premji 2011).
ACKNOWLEDGEMENTS
We are grateful to Dr P. Gupta, Editor, Indian Paediatrics.
We would like to acknowledge the significant contributions of Dr.
AUTHORS’ CONCLUSIONS Peter McEwan to previous versions of this review.
REFERENCES
References to studies included in this review Pyati 1976 {published data only}
Pyati S, Ramamurthy R, Pildes R. Continuous drip
Drew 1979 {published data only} nasogastric feedings: a controlled study (Abstract). Pediatric
Drew JH, Johnston R, Finocchiaro C, Taylor PS, Goldberg Research 1976;10:359.
HJ. A comparison of nasojejunal with nasogastric feedings Roy 1977 {published data only}
in low-birth-weight infants. Australian Paediatric Journal Roy RN, Pollnitz RP, Hamilton JR, Chance GW. Impaired
1979;15(2):98–100. assimilation of nasojejunal feeds in healthy low birth-
Laing 1986 {published data only} weight-infants. Journal of Pediatrics 1977;90(3):431–4.
Laing IA, Lang MA, Callaghan O, Hume R. Nasogastric Van Caillie 1975 {published data only}
compared with nasoduodenal feeding in low birth weight Caillie MV, Powell GK. Nasoduodenal versus nasogastric
infants. Archives of Disease in Childhood 1986;61(2): feeding in the very low birth weight infant. Pediatrics 1975;
138–41. 56(6):1065–72.
Macdonald 1992 {published data only} Wells 1975 {published data only}
Macdonald PD, Skeoch CH, Carse H, Dryburgh F, Wells DH, Zachman RD. Nasojejunal feedings in low-
Alroomi LG, Galea P, et al.Randomised trial of continuous birth-weight infants. Journal of Pediatrics 1975;87(2):
nasogastric, bolus nasogastric, and transpyloric feeding in 276–9.
infants of birth weight under 1400 g. Archives of Disease in Whitfield 1982 {published data only}
Childhood 1992;67(4 Spec No):429–31. Whitfield MF. Poor weight gain of the low birthweight
Pereira 1981 {published data only} infant fed nasojejunally. Archives of Disease in Childhood
Pereira GR, Lemons JA. Controlled study of transpyloric 1982;57(8):597–601.
and intermittent gavage feeding in the small preterm infant. References to studies excluded from this review
Pediatrics 1981;67(1):68–72.
Agarwal 1980 {published data only} Di Fiore 2005
Agarwal RK, Jindal N. Nasojejunal and nasoduodenal tube Di Fiore JM, Arko M, Whitehouse M, Kimball A, Martin
feeding. Indian Pediatrics 1980;17(5):472–5. RJ. Apnea is not prolonged by acid gastroesophageal reflux
in preterm infants. Pediatrics 2005;116(5):1059–63.
Avery 1977 {published data only}
[PUBMED: 16263989]
Avery GB. Nasoduodenal vs. nasogastric feeding. Pediatrics
1977;60(4):550–1. Malcolm 2009
Malcolm WF, Smith PB, Mears S, Goldberg RN, Cotten
Boros 1974 {published data only}
CM. Transpyloric tube feeding in very low birthweight
Boros SJ, Reynolds JW. Duodenal perforation: a
infants with suspected gastroesophageal reflux: impact on
complication of neonatal nasojejunal feeding. Journal of
apnea and bradycardia. Journal of Perinatology 2009;29(5):
Pediatrics 1974;85(1):107–8.
372–5. [PUBMED: 19242488]
Celestin 1978 {published data only} Milner 1981
Celestin LR. Nasojejunal feeding. Lancet 1978;2(8097): Milner RD, Minoli I, Moro G, Rubecz I, Whitfield MF,
992–3. Assan R. Growth and metabolic and hormonal profiles
Cheek 1973 {published data only} during transpyloric and nasogastric feeding in preterm
Cheek JA Jr, Staub GF. Nasojejunal alimentation for infants. Acta Paediatrica Scandanavia 1981;70(1):9–13.
premature and full-term newborn infants. Journal of Misra 2007
Pediatrics 1973;82(6):955–62. Misra S, Macwan K, Albert V. Transpyloric feeding in
Chen 1974 {published data only} gastroesophageal-reflux-associated apnea in premature
Chen JW, Wong PW. Intestinal complications of nasojejunal infants. Acta Paediatrica 2007;96(10):1426–9. [PUBMED:
feeding in low-birth-weight infants. Journal of Pediatrics 17850402]
1974;85(1):109–10. Peter 2002
Price 1978 {published data only} Peter CS, Sprodowski N, Bohnhorst B, Silny J, Poets
Price E, Gyotoku S. Using the nasojejunal feeding technique CF. Gastroesophageal reflux and apnea of prematurity:
in a neonatal intensive care unit. MCN. The American no temporal relationship. Pediatrics 2002;109(1):8–11.
Journal of Maternal Child Nursing 1978;3(6):361–5. [PUBMED: 11773535]
Premji 2011
Uauy 1975 {published data only}
Premji SS, Chessell L. Continuous nasogastric milk feeding
Uauy R, Loo S, Gross I, Warshaw J. Nasojejunal feeding in
versus intermittent bolus milk feeding for premature
the small premature infant: a controlled trial (Abstract).
infants less than 1500 grams. Cochrane Database of
Pediatric Research 1975;9:309.
Systematic Reviews 2011, Issue 11. [DOI: 10.1002/
Valman 1973 {published data only} 14651858.CD001819.pub2]
Valman HB, Brown RJ. Intragastric versus nasojejunal
Raine 1982
feeding of low-birth-weigh infants (Letter). Journal of
Raine PA, Goel KM, Young DG, Galea P, McLaurin JC,
Pediatrics 1973;83(6):1095–6.
Ford JA, et al.Pyloric stenosis and transpyloric feeding.
Wolfsdorf 1975 {published data only} Lancet 1982;2(8302):821–2.
Wolfsdorf J, Makarawa S, Fernandes C, Fenner A. Vazquez 1980
Transpyloric feeding in small preterm infants. Archives of Vazquez C, Arroyos A, Vallis IS. Necrotising enterocolitis.
Disease in Childhood 1975;50(9):723–6. Increased incidence in infants receiving nasoduodenal
feeding. Archives of Disease in Childhood 1980;55(10):826.
Additional references
Vinocur 1990
Berseth 1989 Vinocur P, Stine MJ. Risk factors for late onset necrotising
Berseth CL. Gestational evolution of small intestine motility enterocolitis. Indiana Medicine 1990;83(7):478–80.
in preterm and term infants. Journal of Pediatrics 1989;115
(4):646–51.
References to other published versions of this review
Corvaglia 2009 McGuire 2002
Corvaglia L, Zama D, Gualdi S, Ferlini M, Aceti A, McGuire W, McEwan P. Transpyloric versus gastric
Faldella G. Gastro-oesophageal reflux increases the number tube feeding for preterm infants. Cochrane Database
of apnoeas in very preterm infants. Archives of Disease of Systematic Reviews 2002, Issue 3. [DOI: 10.1002/
in Childhood. Fetal and Neonatal Edition 2009;94(3): 14651858.CD003487]
F188–92. [PUBMED: 18786960] McGuire 2007
Dellagrammaticas 1983 McGuire W, McEwan P. Transpyloric versus gastric
Dellagrammaticas HD, Duerden BI, Milner RD. Upper tube feeding for preterm infants. Cochrane Database
intestinal bacterial flora during transpyloric feeding. of Systematic Reviews 2007, Issue 3. [DOI: 10.1002/
Archives of Disease in Childhood 1983;58(2):115–19. 14651858.CD003487.pub2]

∗
Indicates the major publication for the study
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Drew 1979
Methods Quasi-randomised controlled trial
Participants 66 appropriate for gestational age infants of birth weight < 1500 g
Infants who were receiving assisted ventilation were not included
Interventions Nasojejunal (N = 32) versus nasogastric feeding (N = 34) until achieving an enteral
intake of 200 ml/kg/day
Outcomes Gain in weight, length, and head circumference prior to hospital discharge, calorie intake,
and adverse events (including death, necrotising enterocolitis, intestinal perforation, and
aspiration pneumonia)
Notes Setting: University of Melbourne, Australia, 1974-1977
Risk of bias
Bias Authors’ judgement Support for judgement
Random sequence generation (selection High risk Alternate allocation

bias)
Allocation concealment (selection bias) High risk Alternate allocation
Blinding (performance bias and detection High risk Unblinded

bias)
All outcomes
Incomplete outcome data (attrition bias) High risk Nasojejunal group: 11 infants withdrawn after al-
All outcomes location; 1 required assisted ventilation, 10 because
of failure to pass the feeding tube
Nasogastric group: 11 infants withdrawn after al-
location; 5 required assisted ventilation, 4 died
within 24 hours, 2 had “insufficient data to com-
pute”

Laing 1986
Participants 100 infants allocated, of whom 80 were included. These were infants of birth weight <
1500 g (and appropriate for gestational age - between the 10th and the 90th centile for
birth weight)
Interventions Continuous nasoduodenal (N = 45) versus intermittent nasogastric tube feeding (N =

35) for 7 weeks
Outcomes Weight and length gain, head growth prior to hospital discharge, and adverse events
(including death, necrotising enterocolitis, intestinal perforation, and aspiration pneu-
monia)
Notes Setting: University of Edinburgh, 1982-1984

There were statistically significant differences in the baseline characteristics of the 2
cohorts that may have affected clinical outcomes. The group of infants who were allocated
to nasoduodenal feeding were of statistically significantly lower gestational age, and had
statistically significantly lower Apgar scores at 1 minute and at 5 minutes. It seems
unlikely that these differences were due to chance. We consider that because of the lack
of allocation concealment it is likely that some of the less mature and sicker infants were
allocated preferentially to nasoduodenal feeding
Risk of bias

bias)

bias)
All outcomes
Incomplete outcome data (attrition bias) High risk Growth data were reported only for infants who
All outcomes had successfully tolerated the allocated feeding
route: 16 of the 45 infants allocated to the naso-
duodenal route, and 25 of the 35 infants allocated
to the nasogastric route
In this review, the data on adverse events on all
80 infants included have been extracted from the
report

Macdonald 1992
Methods Randomised controlled trial
Participants 43 infants of birth weight < 1400 g

Infants fed with expressed human breast milk were excluded from the trial
Interventions Continuous nasoduodenal tube feeding (N = 15) versus bolus nasogastric (N = 15) or
continuous nasogastric (N = 13) tube feeding until a weight of 1600 g was attained
Outcomes Gain in weight, head circumference, and length in surviving infants until 36 weeks ges-
tation, calorie intake, time to achieve enteral feeding, plasma albumin, transferrin, urea,
and alkaline phosphatase levels, and adverse events (including necrotising enterocolitis,
intestinal perforation, and aspiration pneumonia)
Notes Setting: University of Glasgow, late 1980s

The data from the bolus nasogastric and continuous nasogastric feeding groups have
been combined in this review
The number of infants who died in each group is reported. Growth data are reported
only for those infants who survived to the end of the study period
Transpyloric group: 15 infants allocated
- 10 infants completed study - growth data available
- 3 infants died before milk feeding established - no growth data available
- 1 infant transferred to another hospital - no growth data available
- 1 infant failure to position tube - no growth data available
Nasogastric group: 28 infants (13 in the continuous NG feed group, 15 in the bolus
NG feed group)
- 24 “completed study” - growth data available
- 3 infants died before milk feeding established - no growth data available
- 1 infant transferred to another hospital - no growth data available
Risk of bias
Random sequence generation (selection Unclear risk Not stated

bias)
Allocation concealment (selection bias) Low risk Sealed envelopes containing random sequence

bias)
All outcomes
Incomplete outcome data (attrition bias) Low risk Near-complete follow-up; see notes above
All outcomes

Pereira 1981
Participants 53 infants of birth weight < 1700 g or gestational age < 33 completed weeks
Interventions Continuous nasojejunal (N = 26) versus intermittent nasogastric tube feeding (N = 27)
until breast feeding was established
Outcomes Weight gain and head growth prior to hospital discharge, calorie intake, and adverse
events (including death, necrotising enterocolitis, intestinal perforation, and aspiration
pneumonia)
Notes Setting: University of Colorado, late 1970s

There were not any standard deviations reported with the growth velocity data
Risk of bias
Random sequence generation (selection Unclear risk Not reported

bias)
Allocation concealment (selection bias) Unclear risk Not reported

bias)
All outcomes
Incomplete outcome data (attrition bias) Low risk Near-complete follow-up

All outcomes
Pyati 1976
Participants 19 infants of birth weight < 1500 g. All participants were of birth weight “appropriate
for gestational age”
Interventions Continuous nasojejunal (N = 8) versus nasogastric feeding (N = 11) with standard-calorie

formula milk started within 30 hours after birth and continued until 3 weeks after birth
Outcomes Calorie intake and weight gain until 3 weeks after birth
Notes Setting: Chicago Medical School, early 1970s

There were limited numerical data reported. We have not been able to contact the
investigators to obtain any unpublished data
Risk of bias

Pyati 1976 (Continued)

bias)

bias)
All outcomes
Incomplete outcome data (attrition bias) Low risk Near-complete follow-up

All outcomes
Roy 1977
Participants 21 infants of birth weight < 1500 g and appropriate for gestational age
Infants who required assisted ventilation or phototherapy were excluded

for 7 days
Outcomes Gain in weight, length, and skinfold thickness prior to hospital discharge, and stool
frequency
Notes Setting: University of Toronto, early 1970s

3 infants in the nasojejunal tube feeding group who developed complications were with-
drawn, and not included in the growth comparison
1 infant was withdrawn because of persistent displacement of the tube back to the
stomach. A second infant developed “transitory but extensive abdominal distention”.
Since it is unclear whether this complication resulted in cessation of enteral feeding,
we have not classified this as an adverse event. The third infant developed peritonitis
following duodenal perforation (confirmed at laparotomy)
Risk of bias

bias)

bias)
All outcomes
Roy 1977 (Continued)
All outcomes
Van Caillie 1975
Participants 11 preterm infants of birthweight < 1300 g
Interventions Allocated alternately to continuous nasoduodenal (N = 6) versus continuous nasogastric

tube feeding (N = 5) for 40 days
Outcomes Weight gain prior to hospital discharge, calorie intake, adverse events (including death,
necrotising enterocolitis, intestinal perforation, and aspiration pneumonia)
Notes Setting: University of Texas, USA. Early 1970s

The report gives outcome data on all infants who entered the study. However, one of
the infants who had been allocated to nasoduodenal feeding died at aged 30 hours.
This infant was included in the analysis of adverse outcomes, but not included in the
calculations of short-term growth parameters presented by the investigators
Risk of bias

bias)

bias)
All outcomes
All outcomes
Wells 1975
Participants 22 infants of birth weight < 500 g and of gestational age < 32 completed weeks
for 21 days

Wells 1975 (Continued)
Outcomes Weight gain for the 21-day study period, calorie intake, and adverse events (death,
necrotising enterocolitis)
Notes Setting: Wisconsin Perinatal Center, early 1970s

3 of the infants who had been allocated to the nasogastric feeding group were switched
during the study to nasojejunal feeding because of concern about the level of calorie
intake. These infants were not included in the analysis of growth rates. There were
insufficient data for 1 other infant, who had been allocated to nasojejunal feeding, to be
included in the analysis of growth outcomes presented in the report
Risk of bias

bias)

bias)
All outcomes
All outcomes
Whitfield 1982
Methods Quasi-randomised controlled trial (alternate months)
Participants 44 appropriate for gestational age preterm infants of birth weight 1000 to 1500 g
until attaining a weight of 1500 g
Outcomes Weight gain and head growth until 6 months old, and adverse events (death, necrotising
enterocolitis, intestinal perforation)
Notes Setting: University of Sheffield. Late 1970s

1. Short-term weight gain data are presented for only those infants with birth weight less
than 1.4 kg - i.e. these data are not presented for infants of birth weight 1.4 to 1.5 kg
- Transpyloric group: 20 infants
- NG group: 10 infants
2. Longer-term growth data: presented for infants for whom a weight at the expected
data of delivery was available:
At EDD:
- Transpyloric group: 21 infants available for follow-up (4 infants had died, 2 infants

Whitfield 1982 (Continued)
had been transferred to another hospital, 1 infant had been “withdrawn” because of
“intractable abdominal distension”, and the reason for the non-availability of the unac-
counted for infant is unclear from the report)
- NG group: 15 infants available for follow-up (1 infant had been transferred to another
hospital)
At EDD +3 months - further loss to follow-up occurred, leaving:
- Transpyloric group: 18 infants available for evaluation
- NG group: 15 infants available for evaluation
At EDD + 6 months - further loss to follow-up occurred, leaving:
- Transpyloric group: 16 infants available for evaluation
- NG group: 15 infants available for evaluation
Risk of bias
Random sequence generation (selection High risk Alternate monthly allocation

bias)
Allocation concealment (selection bias) High risk Alternate monthly allocation

bias)
All outcomes
All outcomes
EDD: expected date of delivery

NG: nasogastric
Characteristics of excluded studies [ordered by study ID]
Study Reason for exclusion
Agarwal 1980 Although not apparent from the title, this is not a report of either a randomised or quasi-randomised trial
Avery 1977 Although not apparent from the title, this is not a report of either a randomised or quasi-randomised trial
Boros 1974 Although not apparent from the title, this is not a report of either a randomised or quasi-randomised trial
Celestin 1978 Although not apparent from the title, this is not a report of either a randomised or quasi-randomised trial
Cheek 1973 Although not apparent from the title, this is not a report of either a randomised or quasi-randomised trial

(Continued)
Chen 1974 Although not apparent from the title, this is not a report of either a randomised or quasi-randomised trial
Price 1978 Although not apparent from the title, this is not a report of either a randomised or quasi-randomised trial
Uauy 1975 Reported as an abstract only, this is described as a “controlled study”, but is unlikely to represent a report of a
randomised or quasi-randomised trial
Valman 1973 Although not apparent from the title, this is not a report of either a randomised or quasi-randomised trial
Wolfsdorf 1975 Although not apparent from the title or abstract, this is not a report of a randomised or quasi-randomised trial

DATA AND ANALYSES
Comparison 1. Transpyloric versus gastric tube feeding for preterm infants: growth
No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size
1 Change in weight (g/week) 4 93 Mean Difference (IV, Fixed, 95% CI) -5.50 [-26.88, 15.
89]
2 Change in crown heel length 3 93 Mean Difference (IV, Fixed, 95% CI) -0.67 [-2.36, 1.02]
(mm/week)
3 Change in occipito-frontal head 2 75 Mean Difference (IV, Fixed, 95% CI) 0.56 [-0.95, 2.08]
circumference (mm/week)
4 Change in subscapular skinfold 1 18 Mean Difference (IV, Fixed, 95% CI) -0.20 [-1.18, 0.78]
thickness (mm/week)
Comparison 2. Transpyloric versus gastric tube feeding for preterm infants: adverse events
No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size
1 Death prior to hospital discharge 6 245 Risk Ratio (M-H, Fixed, 95% CI) 2.46 [1.36, 4.46]
2 Death prior to hospital discharge 5 165 Risk Ratio (M-H, Fixed, 95% CI) 2.19 [0.89, 5.35]
(excluding Laing 1986)
3 Gastrointestinal disturbance 7 297 Risk Ratio (M-H, Fixed, 95% CI) 1.48 [1.05, 2.09]
(including diarrhoea) prior to
hospital discharge
4 Gastrointestinal disturbance 6 217 Risk Ratio (M-H, Fixed, 95% CI) 1.43 [1.02, 2.01]
(including diarrhoea) prior to
hospital discharge (excluding
Laing 1986)
5 Necrotising enterocolitis prior to 7 298 Risk Ratio (M-H, Fixed, 95% CI) 0.63 [0.26, 1.53]
hospital discharge
6 Necrotising enterocolitis prior to 6 218 Risk Ratio (M-H, Fixed, 95% CI) 0.91 [0.32, 2.58]
hospital discharge (excluding
Laing 1986)
7 Aspiration pneumonia prior to 5 171 Risk Ratio (M-H, Fixed, 95% CI) 1.35 [0.44, 4.14]
hospital discharge
8 Intestinal perforation prior to 4 129 Risk Ratio (M-H, Fixed, 95% CI) 2.31 [0.10, 50.85]
hospital discharge

Analysis 1.1. Comparison 1 Transpyloric versus gastric tube feeding for preterm infants: growth, Outcome
1 Change in weight (g/week).
Review: Transpyloric versus gastric tube feeding for preterm infants
Comparison: 1 Transpyloric versus gastric tube feeding for preterm infants: growth
Outcome: 1 Change in weight (g/week)
Mean Mean
Study or subgroup Transpyloric tube Gastric tube Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Macdonald 1992 10 158 (60) 24 162 (49) 25.9 % -4.00 [ -46.04, 38.04 ]
Roy 1977 9 79 (31) 9 88 (41) 40.6 % -9.00 [ -42.58, 24.58 ]
Van Caillie 1975 6 112 (51) 5 70 (62) 9.9 % 42.00 [ -25.96, 109.96 ]
Whitfield 1982 20 65 (65) 10 86 (54) 23.7 % -21.00 [ -64.95, 22.95 ]
Total (95% CI) 45 48 100.0 % -5.50 [ -26.88, 15.89 ]

Heterogeneity: Chi2 = 2.40, df = 3 (P = 0.49); I2 =0.0%
Test for overall effect: Z = 0.50 (P = 0.61)
Test for subgroup differences: Not applicable
-100 -50 0 50 100

Favours gastric tube Favours transpyloric

2 Change in crown heel length (mm/week).
Outcome: 2 Change in crown heel length (mm/week)
Mean Mean
Laing 1986 16 7 (4) 25 8 (2) 63.9 % -1.00 [ -3.11, 1.11 ]
Macdonald 1992 10 11 (4) 24 11 (4) 32.7 % 0.0 [ -2.95, 2.95 ]
Roy 1977 9 6 (10) 9 7 (10) 3.3 % -1.00 [ -10.24, 8.24 ]
Total (95% CI) 35 58 100.0 % -0.67 [ -2.36, 1.02 ]

-10 -5 0 5 10

3 Change in occipito-frontal head circumference (mm/week).
Outcome: 3 Change in occipito-frontal head circumference (mm/week)
Mean Mean
Laing 1986 16 8 (4) 25 8 (3) 44.0 % 0.0 [ -2.29, 2.29 ]
Macdonald 1992 10 11 (3) 24 10 (2) 56.0 % 1.00 [ -1.02, 3.02 ]
Total (95% CI) 26 49 100.0 % 0.56 [ -0.95, 2.08 ]

-2 -1 0 1 2
4 Change in subscapular skinfold thickness (mm/week).
Outcome: 4 Change in subscapular skinfold thickness (mm/week)
Mean Mean
Roy 1977 9 0.1 (0.1) 9 0.3 (1.5) 100.0 % -0.20 [ -1.18, 0.78 ]
Total (95% CI) 9 9 100.0 % -0.20 [ -1.18, 0.78 ]

Heterogeneity: not applicable
-1 -0.5 0 0.5 1

Analysis 2.1. Comparison 2 Transpyloric versus gastric tube feeding for preterm infants: adverse events,
Outcome 1 Death prior to hospital discharge.
Comparison: 2 Transpyloric versus gastric tube feeding for preterm infants: adverse events
Outcome: 1 Death prior to hospital discharge
Study or subgroup Transpyloric tube Gastric tube Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Drew 1979 3/21 1/23 7.3 % 3.29 [ 0.37, 29.20 ]
Laing 1986 21/45 6/35 51.9 % 2.72 [ 1.23, 6.01 ]
Macdonald 1992 3/15 3/28 16.1 % 1.87 [ 0.43, 8.14 ]
Van Caillie 1975 1/7 0/5 4.4 % 2.25 [ 0.11, 46.13 ]
Wells 1975 2/11 2/11 15.4 % 1.00 [ 0.17, 5.89 ]
Whitfield 1982 4/28 0/16 4.8 % 5.28 [ 0.30, 92.10 ]
Total (95% CI) 127 118 100.0 % 2.46 [ 1.36, 4.46 ]

Total events: 34 (Transpyloric tube), 12 (Gastric tube)
0.01 0.1 1 10 100

Favours transpyloric Favours gastric tube

Outcome 2 Death prior to hospital discharge (excluding Laing 1986).
Outcome: 2 Death prior to hospital discharge (excluding Laing 1986)
Drew 1979 3/21 1/23 15.3 % 3.29 [ 0.37, 29.20 ]
Macdonald 1992 3/15 3/28 33.5 % 1.87 [ 0.43, 8.14 ]
Van Caillie 1975 1/7 0/5 9.1 % 2.25 [ 0.11, 46.13 ]
Wells 1975 2/11 2/11 32.0 % 1.00 [ 0.17, 5.89 ]
Whitfield 1982 4/28 0/16 10.1 % 5.28 [ 0.30, 92.10 ]
Total (95% CI) 82 83 100.0 % 2.19 [ 0.89, 5.35 ]

0.01 0.1 1 10 100


Outcome 3 Gastrointestinal disturbance (including diarrhoea) prior to hospital discharge.
Outcome: 3 Gastrointestinal disturbance (including diarrhoea) prior to hospital discharge
Drew 1979 5/21 7/23 24.8 % 0.78 [ 0.29, 2.09 ]
Laing 1986 2/45 0/35 2.1 % 3.91 [ 0.19, 78.98 ]
Macdonald 1992 4/15 1/28 2.6 % 7.47 [ 0.91, 60.95 ]
Pereira 1981 22/26 17/27 61.8 % 1.34 [ 0.96, 1.87 ]
Roy 1977 1/12 0/9 2.1 % 2.31 [ 0.10, 50.85 ]
Van Caillie 1975 3/7 1/5 4.3 % 2.14 [ 0.30, 15.07 ]
Whitfield 1982 1/28 0/16 2.3 % 1.76 [ 0.08, 40.80 ]
Total (95% CI) 154 143 100.0 % 1.48 [ 1.05, 2.09 ]

0.01 0.1 1 10 100


Outcome 4 Gastrointestinal disturbance (including diarrhoea) prior to hospital discharge (excluding Laing
1986).
Outcome: 4 Gastrointestinal disturbance (including diarrhoea) prior to hospital discharge (excluding Laing 1986)
Drew 1979 5/21 7/23 25.3 % 0.78 [ 0.29, 2.09 ]
Macdonald 1992 4/15 1/28 2.6 % 7.47 [ 0.91, 60.95 ]
Pereira 1981 22/26 17/27 63.1 % 1.34 [ 0.96, 1.87 ]
Roy 1977 1/12 0/9 2.1 % 2.31 [ 0.10, 50.85 ]
Van Caillie 1975 3/7 1/5 4.4 % 2.14 [ 0.30, 15.07 ]
Whitfield 1982 1/28 0/16 2.4 % 1.76 [ 0.08, 40.80 ]
Total (95% CI) 109 108 100.0 % 1.43 [ 1.02, 2.01 ]

0.01 0.1 1 10 100


Outcome 5 Necrotising enterocolitis prior to hospital discharge.
Outcome: 5 Necrotising enterocolitis prior to hospital discharge
Drew 1979 2/21 1/23 8.5 % 2.19 [ 0.21, 22.43 ]
Laing 1986 1/45 4/35 39.9 % 0.19 [ 0.02, 1.66 ]
Macdonald 1992 2/15 2/28 12.4 % 1.87 [ 0.29, 11.95 ]
Pereira 1981 0/26 3/27 30.4 % 0.15 [ 0.01, 2.73 ]
Van Caillie 1975 0/7 0/5 Not estimable
Wells 1975 1/11 1/11 8.9 % 1.00 [ 0.07, 14.05 ]
Whitfield 1982 0/28 0/16 Not estimable
Total (95% CI) 153 145 100.0 % 0.63 [ 0.26, 1.53 ]

Heterogeneity: Chi2 = 4.64, df = 4 (P = 0.33); I2 =14%
0.01 0.1 1 10 100


Outcome 6 Necrotising enterocolitis prior to hospital discharge (excluding Laing 1986).
Outcome: 6 Necrotising enterocolitis prior to hospital discharge (excluding Laing 1986)
Drew 1979 2/21 1/23 14.1 % 2.19 [ 0.21, 22.43 ]
Macdonald 1992 2/15 2/28 20.6 % 1.87 [ 0.29, 11.95 ]
Pereira 1981 0/26 3/27 50.6 % 0.15 [ 0.01, 2.73 ]
Wells 1975 1/11 1/11 14.7 % 1.00 [ 0.07, 14.05 ]
Total (95% CI) 108 110 100.0 % 0.91 [ 0.32, 2.58 ]

0.01 0.1 1 10 100

Favours transpyloric Favours gastric

Outcome 7 Aspiration pneumonia prior to hospital discharge.
Outcome: 7 Aspiration pneumonia prior to hospital discharge
Drew 1979 1/21 0/23 10.6 % 3.27 [ 0.14, 76.21 ]
Macdonald 1992 2/15 1/28 15.4 % 3.73 [ 0.37, 37.88 ]
Pereira 1981 1/26 0/27 10.9 % 3.11 [ 0.13, 73.09 ]
Pyati 1976 0/8 0/11 Not estimable
Van Caillie 1975 0/7 2/5 63.2 % 0.15 [ 0.01, 2.58 ]
Total (95% CI) 77 94 100.0 % 1.35 [ 0.44, 4.14 ]

Heterogeneity: Chi2 = 3.60, df = 3 (P = 0.31); I2 =17%
0.01 0.1 1 10 100


Outcome 8 Intestinal perforation prior to hospital discharge.
Outcome: 8 Intestinal perforation prior to hospital discharge
Pereira 1981 0/26 0/27 Not estimable
Roy 1977 1/12 0/9 100.0 % 2.31 [ 0.10, 50.85 ]
Total (95% CI) 72 57 100.0 % 2.31 [ 0.10, 50.85 ]

Heterogeneity: not applicable
0.02 0.1 1 10 50
WHAT’S NEW
Last assessed as up-to-date: 30 June 2012.
Date Event Description
18 July 2012 New search has been performed This updates the review ’Transpyloric versus gastric tube
feeding for preterm infants’ (McGuire 2007).
Search updated in June 2012. No new trials identified.
The ’Background’ and ’Discussion’ sections have been up-
dated to include discussion of the possible role of transpy-
loric feeding in preventing gastro-oesophageal reflux-at-
tributed apnoea/bradycardia
18 July 2012 New citation required but conclusions have not changed New author added - Dr Julie Watson.
No change to conclusions of review.

HISTORY
Protocol first published: Issue 1, 2002
Review first published: Issue 3, 2002
Date Event Description
20 March 2007 New search has been performed This review updates ’Transpyloric versus gastric tube
feeding for preterm infants’, published in the Cochrane
Database of Systematic Reviews, The Cochrane Library,
Issue 3, 2002 (McGuire 2002).
Our electronic search was updated in June 2012. No

new trials were eligible for this updated search.
We re-classified one study that was reported as an abstract

only from ’excluded’ to ’included’, as it is clear that this
trial was randomised. Inclusion of this small trial did not
change any of the conclusions of the review
20 March 2007 New citation required but conclusions have not changed Substantive amendment
CONTRIBUTIONS OF AUTHORS
Julie Watson, Peter McEwan, and William McGuire revised the protocol, undertook the electronic and handsearches, and screened
the title and abstract of identified studies, and the full text of potentially relevant reports. Two authors independently assessed the
methodological quality of the included trials, extracted the relevant information and data, and completed the final review.
2012 update completed by Julie Watson and William McGuire.
DECLARATIONS OF INTEREST
None
SOURCES OF SUPPORT
Internal sources
• Tayside Institute of Child Health, Ninewells Hospital and Medical School, Dundee, UK.

External sources
• Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health,
Department of Health and Human Services, USA.
Editorial support of the Cochrane Neonatal Review Group has been funded with Federal funds from the Eunice Kennedy Shriver
National Institute of Child Health and Human Development National Institutes of Health, Department of Health and Human
Services, USA, under Contract No. HHSN275201100016C.
INDEX TERMS
Medical Subject Headings (MeSH)

∗ Infant, Premature; Enteral Nutrition [adverse effects; ∗ methods]; Infant, Newborn; Pylorus; Randomized Controlled Trials as Topic
MeSH check words

Humans


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Cochrane Database of Systematic Reviews

Transpyloric versus gastric tube feeding for preterm infants

Transpyloric versus gastric tube feeding for preterm infants (Review)

Transpyloric versus gastric tube feeding for preterm infants (Review) i

Transpyloric versus gastric tube feeding for preterm infants

Julie Watson1 , William McGuire2

Editorial group: Cochrane Neonatal Group.

PLAIN LANGUAGE SUMMARY

Transpyloric versus gastric tube feeding for preterm infants

BACKGROUND Why it is important to do this review

Description of the intervention

Transpyloric versus gastric tube feeding for preterm infants (Review) 3

Transpyloric versus gastric tube feeding for preterm infants (Review) 4

Transpyloric versus gastric tube feeding for preterm infants (Review) 5

b. Short-term linear growth (Outcome 1.2)

MD 0.6 (95% CI -0.9 to 2.1) mm/week.

Transpyloric versus gastric tube feeding for preterm infants (Review) 7

Transpyloric versus gastric tube feeding for preterm infants (Review) 8

In a sensitivity analysis (Outcome 2.4), removing Laing 1986,

3. Necrotising enterocolitis (Outcome 2.5) 5. Intestinal perforation (Outcome 2.8)

4. Aspiration pneumonia/pneumonitis (Outcome 2.7)

Transpyloric versus gastric tube feeding for preterm infants (Review) 9

Transpyloric versus gastric tube feeding for preterm infants (Review) 12

Characteristics of included studies [ordered by study ID]

Methods Quasi-randomised controlled trial

Notes Setting: University of Melbourne, Australia, 1974-1977

Bias Authors’ judgement Support for judgement

Random sequence generation (selection High risk Alternate allocation

Allocation concealment (selection bias) High risk Alternate allocation

Blinding (performance bias and detection High risk Unblinded

Transpyloric versus gastric tube feeding for preterm infants (Review) 13

Methods Quasi-randomised controlled trial

Interventions Continuous nasoduodenal (N = 45) versus intermittent nasogastric tube feeding (N =

Notes Setting: University of Edinburgh, 1982-1984

Bias Authors’ judgement Support for judgement

Random sequence generation (selection High risk Alternate allocation

Allocation concealment (selection bias) High risk Alternate allocation

Blinding (performance bias and detection High risk Unblinded

Transpyloric versus gastric tube feeding for preterm infants (Review) 14

Methods Randomised controlled trial

Participants 43 infants of birth weight < 1400 g

Notes Setting: University of Glasgow, late 1980s

Bias Authors’ judgement Support for judgement

Random sequence generation (selection Unclear risk Not stated

Blinding (performance bias and detection High risk Unblinded

Transpyloric versus gastric tube feeding for preterm infants (Review) 15

Methods Randomised controlled trial

Notes Setting: University of Colorado, late 1970s

Bias Authors’ judgement Support for judgement

Random sequence generation (selection Unclear risk Not reported

Allocation concealment (selection bias) Unclear risk Not reported

Blinding (performance bias and detection High risk Unblinded

Incomplete outcome data (attrition bias) Low risk Near-complete follow-up

Methods Randomised controlled trial

Interventions Continuous nasojejunal (N = 8) versus nasogastric feeding (N = 11) with standard-calorie

Notes Setting: Chicago Medical School, early 1970s

Transpyloric versus gastric tube feeding for preterm infants (Review) 16

Bias Authors’ judgement Support for judgement

Random sequence generation (selection Unclear risk Not reported

Allocation concealment (selection bias) Unclear risk Not reported

Blinding (performance bias and detection High risk Unblinded

Incomplete outcome data (attrition bias) Low risk Near-complete follow-up

Methods Randomised controlled trial