Description of the condition
The establishment of safe oral feeding in preterm or low birth weight infants may be delayed because of poor co-ordination of sucking and swallowing, neurological immaturity and respiratory distress.
Description of the intervention
Enteral feeds may be delivered through a catheter (feeding tube) passed via the nose or via the mouth into the stomach or upper small intestine. There are potential advantages and disadvantages to both the nasal and oral routes for enteral feeding tube placement. Policy and practice varies between and within neonatal care units (Shiao 1996; Birnbaum 2009; Gregory 2012).
How the intervention might work
Enteral feeding tubes passed via the nose are easier to secure to the face than orally placed tubes. However, since newborn infants are obligate nose breathers, feeding tubes placed via the nose can cause partial nasal obstruction, which increases airway resistance and work of breathing (Stocks 1980; Greenspan 1990). Airway resistance may differ between infants of similar weights due to differences in nasal size and structure. Naso-enteric intubation through the larger nostril may increase airway resistance as the infant is forced to breathe through an airway of smaller calibre. This increase in energy expenditure may potentially affect nutrient requirements and growth.
Orally placed enteral tubes are more frequently malpositioned compared to nasally placed tubes (Ellett 1998). Incorrect placement, or subsequent displacement, of feeding tubes into the lower oesophagus or into the lung can lead to aspiration, respiratory compromise, and increased energy expenditure. Furthermore, orally placed tubes may be easier to displace as they can loop inside the mouth. Repetitive movement of the orally placed tube may result in mucosal trauma and may increase the incidence of apnoea and bradycardia due to vagal stimulation. Similarly, orally placed duodenal and jejunal tubes may be easier to displace proximally, potentially increasing the risk of aspiration and respiratory compromise.
Why it is important to do this review
Given the potential for the route of enteral tube placement to affect important outcomes for preterm or low birth weight infants, we have attempted to detect, appraise and synthesise the available evidence from randomised controlled trials to inform practice and research.
To determine the effect of nasal versus oral placement of enteral feeding tubes on feed tolerance, the incidence of adverse events, and growth and development, in preterm or low birth weight infants.
Criteria for considering studies for this review
Types of studies
Controlled trials using either random or quasi-random patient allocation.
Types of participants
Preterm infants (< 37 weeks' gestation) or low birth weight infants (< 2500 g) receiving enteral tube feeding.
Types of interventions
Trials comparing nasal versus oral placement of enteral feeding tubes. Feeding tubes could have been in place either continuously (indwelling) or placed just for the duration of feeding and removed between feeds provided the same strategy was used for both the nasal and oral placement groups.
Types of outcome measures
- Time to establish full enteral tube feeds independently of parenteral fluids or nutrition (days).
- Adverse events:
- incidence of non-intentional removal or displacement of feeding tube;
- apnoea defined as breathing pauses that last for > 20 seconds or for > 10 seconds if associated with bradycardia or oxygen desaturation (Finer 2006);
- aspiration pneumonia/pneumonitis: clinical, radiological, or both, evidence of lower respiratory tract compromise that has been attributed to covert or evident aspiration of gastric contents.
- Growth: time to re-gain birth weight and subsequent rates of weight gain, linear growth, head growth, or skinfold thickness growth.
- Time to independence from supplemental oxygen (days).
- Time to establish full oral feeds (at least 120 mL/kg/day) (days).
Search methods for identification of studies
We used the standard search strategy of the Cochrane Neonatal Review Group (http://neonatal.cochrane.org/).
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 10, 2012), MEDLINE (1966 to September 2012) and EMBASE (1980 to September 2012). The search strategy used the following text words and Medical Subject Headings: [Infant, Newborn OR Infant, Premature OR Infant, Low Birth Weight OR Infant, Very Low Birth Weight OR neonate$ OR infan$ OR preterm OR low birth weight OR LBW] AND [Enteral Nutrition/methods OR Intubation, Gastrointestinal OR nasogastric OR orogastric]. We used a search filter in MEDLINE and EMBASE to limit retrieval to clinical trials. We did not apply any language restrictions.
Searching other resources
We examined the references in studies identified as potentially relevant. We also searched the abstracts from the annual meetings of the Pediatric Academic Societies (1993 to 2012), the European Academy of Paediatrics (1995 to 2012), the UK Royal College of Paediatrics and Child Health (2000 to 2012) and the Perinatal Society of Australia and New Zealand (2000 to 2012). We considered trials reported only as abstracts to be eligible if sufficient information was available from the report, or from contact with the authors to fulfil the inclusion criteria.
Data collection and analysis
Selection of studies
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 not meet all of the inclusion criteria. We discussed any disagreements until consensus was achieved.
Data extraction and management
We used a data collection form to aid extraction of relevant information from each included study. Two review authors extracted the data separately. We discussed any disagreements until consensus was achieved. We asked the investigators for further information if data from the trial reports were insufficient.
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 any included trials. Additional information from the trial authors was requested to clarify methodology and results as necessary. We evaluated and reported the following issues in the 'Risk of bias' tables:
- Sequence generation: we categorised the method used to generate the allocation sequence as:
- low risk: any random process, for example random number table; computer random number generator;
- high risk: any non-random process, for example odd or even date of birth; patient case-record number;
- Allocation concealment: we categorised the method used to conceal the allocation sequence as:
- low risk: for example telephone or central randomisation; consecutively numbered sealed opaque envelopes;
- high risk: open random allocation; unsealed or non-opaque envelopes, alternation; date of birth;
- Blinding: we assessed blinding of participants, clinicians and caregivers, and outcome assessors separately for different outcomes and categorised the methods as:
- low risk;
- high risk;
- Incomplete outcome data: we described the completeness 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 was reported or supplied by the trial authors, re-included missing data in the analyses. We categorised completeness as:
- low risk: < 20% missing data;
- high risk: ≥ 20% missing data;
Measures of treatment effect
We calculated risk ratio (RR) and risk difference (RD) for dichotomous data and weighted mean difference (WMD) for continuous data with respective 95% confidence intervals (CI). We determined the number needed to treat for an additional beneficial outcome (NNTB) or an additional harmful outcome (NNTH) for a statistically significant RD.
Unit of analysis issues
The unit of analysis is the participating infant in individually randomised trials and the neonatal unit for cluster randomised trials.
Dealing with missing data
We requested missing study data from the trial investigators.
Assessment of heterogeneity
If more than one trial was included in a meta-analysis, we examined the treatment effects of individual trials and heterogeneity between trial results by inspecting the forest plots. We calculated the I
We planned to use a fixed-effect model for meta-analyses.
Subgroup analysis and investigation of heterogeneity
Very low birth weight (< 1.5 kg) or very preterm (< 32 weeks' gestation at birth) infants.
Description of studies
van Someren 1984 enrolled 42 preterm infants who required feeding via an enteral feeding tube. Gestational age at birth ranged from 30 to 34 weeks. Infants were randomised to receive either naso-enteric or oro-enteric feeding. Some of the infants in each group received transpyloric feeds, but the report of the trial does not state how many. The oral feeding tube was secured to the palate with a grooved orthodontic appliance (Sullivan 1981). Infants were recruited to the trial at a postnatal age of between one and 12 days and remained in the study until breast or bottle-feeding had been established. The primary outcome of the trial was the incidence of episodes of periodic breathing and central apnoea assessed by respiratory and polygraphic monitoring on the third and seventh days after randomisation. The investigators also assessed rate of weight gain during the first two weeks of participation, the incidence of local complications such as oral ulceration, and a composite 'sickness score' (mainly a score of the need for and duration of respiratory support).
Dsilna 2005 recruited 46 infants (gestational age < 30 weeks or birth weight < 1200 g) who required feeding via an enteral feeding tube. Infants were randomly allocated to either gavage feeding via a nasogastric or an orogastric tube until 32 weeks' postmenstrual age. Subsequently, all infants were fed via the orogastric route. The outcomes assessed were nutrient intake during the trial period, time to achieve full enteral feeding, time to regain birth weight, and the incidence of various neonatal morbidities (including necrotising enterocolitis).
Bohnhorst 2010 undertook a randomised cross-over (sequential treatment) trial in which 35 spontaneously breathing, very preterm infants (< 32 weeks' gestational age) with evidence of apnoea or bradycardia of prematurity participated. Infants were randomly allocated to either 12 hours of nasogastric or 12 hours of orogastric feeding followed by 12 hours of the alternative feeding route. Thirty-two infants completed the study. The primary outcomes were the incidence of apnoea, desaturation and bradycardia during the study period.
Risk of bias in included studies
Quality assessments are detailed in table 'Characteristics of included studies'.
van Someren 1984: the method of randomisation used was not stated. Caregivers and assessors were not blinded to the intervention. The primary outcomes, respiratory monitoring data recorded either on the third or seventh day, were reported for 69% of the participating infants.
Dsilna 2005: allocation concealment was achieved using sealed opaque envelopes. Caregivers and assessors were not blinded to the intervention. Follow-up was complete.
Bohnhorst 2010: the random sequence was computer-generated but the allocation concealment method was not described. Caregivers were aware of the feeding tube placement route. Respiratory function recording were assessed blind to identity of the infant and the feeding route. Three infants did not complete the study because the frequency of apnoea or bradycardia necessitated respiratory support.
Effects of interventions
Nasal versus oral placement of enteral feeding tubes (Comparison 1)
Time to establish full enteral tube feeds (Outcome 1.1; Analysis 1.1)
Dsilna 2005 did not find a statistically significant difference: MD -2.7 (95% CI -11.9 to 6.5) days after birth. The other trials did not report this outcome.
Adverse events: none of the trials reported the incidence of non-intentional removal or displacement of feeding tube or the incidence of aspiration pneumonia/pneumonitis.
van Someren 1984 did not find any statistically significant differences in the frequency of episodes of apnoea between the groups on the third day post-randomisation. On the seventh day, the nasal placement group had statistically significantly more recorded episodes of apnoea. However, the definition of apnoea was cessation of breathing for 5 seconds or greater rather than the more commonly used definition (cessation of breathing for ≥ 20 seconds) that we pre-specified for this review.
Bohnhorst 2010 did not find any statistically significant differences in the frequency of apnoea, desaturation or bradycardia:
- median (interquartile range) number of bradycardia/desaturation episodes per hour: 1.6 (95% CI 0.8 to 1.9) versus 1.0 (95% CI 0.9 to 1.6);
- median (interquartile range) number of apnoea episodes per hour: 0.8 (95% CI 0.7 to 1.2) versus 0.8 (95% CI 0.5 to 1.2).
Dsilna 2005 did not report the incidence of frequency of apnoea, desaturation or bradycardia.
Growth (Outcome 1.2; Analysis 1.2)
Dsilna 2005 did not find a statistically significant difference in the time taken to regain birth weight: MD 0.90 (95% CI -1.3 to 3.1) days.
van Someren 1984 reported weight gain in the 37 infants who remained in the trial until at least 14 days post randomisation. There was a statistically significantly lower rate of weight gain in the first week after randomisation in the infants fed via naso-enteric feeding tubes (0.6 vs 8.3 g/kg/day). In the second week after randomisation there was not a statistically significant difference (13.6 vs 12.3 g/kg/day).
Time to independence from supplemental oxygen (Outcome 1.3; Analysis 1.3)
Dsilna 2005 did not find a statistically significant difference: MD 7.6 (95% CI -15.2 to 30.4) days. The other trials did not report this outcome.
Time to establish full oral feeds: not reported by any trials.
Subgroup data for very low birth weight or very preterm infants were not available for van Someren 1984.
Summary of main results
There are only limited data available from two small parallel group randomised controlled trials and one cross-over trial on the effect of the nasal versus the oral route for placing feeding tubes in preterm or low birth weight infants. These trials had some methodological limitations including lack of blinding of caregivers and assessors and incomplete follow-up assessment. The trials did not find evidence that the route of placement of enteral feeding tubes affects important outcomes.
Overall completeness and applicability of evidence
The identified trials were small, contained methodological weaknesses, and did not report all important outcomes. None of the trials reported the incidence of non-intentional removal or displacement of feeding tube, yet this is the most commonly expressed anxiety from parents attempting to perform this activity on the neonatal unit or when discharged home with an infant receiving enteral tube feeding (Howell 2011).
We excluded two trials that compared feeding with indwelling nasogastric tubes versus intermittently placed orogastric tubes (Symington 1995; Kublick 2011). This co-intervention (leaving the nasogastric tube in place versus replacing the orogastric tube at each feed) prevents independent assessment of the effects of nasal versus oral tube placement. However, it may be that this comparison is viewed as pragmatic by some clinicians, caregivers and parents and that a separate or subgroup review of trials of these two approaches is merited.
It may also be appropriate to consider whether the route of placement of feeding tubes affects other outcomes including infant distress during placement, and parental views. These might include parental perceptions of ease of placement and security, especially given that infants may be discharged home with a feeding tube in situ (Collins 2003).
Quality of the evidence
The included trials contained various methodological weaknesses (Figure 1).
|Figure 1. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.|
In van Someren 1984, the method of randomisation was not stated so it is possible that allocation was not concealed and the assignment of infants to one or other feeding route could have been predicted. This may have allowed bias in allocation of infants that could have affected the outcomes independently of the intervention. The mean postnatal age of entry into the study was two days for the nasal group compared to six days for the oral group. This difference may have been a factor in the lower rate of weight gain in the nasal group during the first seven days of assessment. More infants in the oral group would have already transitioned through the normal postnatal weight loss that occurs during the first week of postnatal life, whereas many infants in the nasal group were still in this postnatal weight loss phase. The difference in weight gain was not sustained during the second week of the study period. Furthermore, the finding of a difference in the frequency of apnoea identified on the seventh day after entry into the trial should also be interpreted cautiously. Follow-up assessment was incomplete and the definition of apnoea used in the trial was different from that of consensus agreements of the definition of clinically significant apnoea. Finally, oral placement of the feeding tube relied on the use of a palatal appliance to secure the tube thus limiting the applicability of the study findings to the more common practice of securing orally placed tubes at the lips.
The second parallel group trial was more methodologically rigorous but assessed only short-term outcomes (Dsilna 2005). The trial did not provide any evidence of effect on the time taken to establish enteral feeds, weight gain during the early neonatal period, or time taken to wean from oxygen supplementation. However, only 46 infants in total participated and the trial was underpowered to exclude modest but plausible effect sizes.
The cross-over trial used a computer-generated random sequence to determine the sequence in which infant received naso-enteric versus oro-enteric feeding (Bohnhorst 2010). The method of allocation concealment was not stated but this may be less important as a source of bias given that all infants received both interventions and acted as their own 'internal' controls. Caregivers were aware of the feeding route but the assessment of respiratory monitor recordings was undertaken blind to the identity of the infant and the feeding route. Although 32 of 35 infants completed the assessment, the three excluded infants all had episodes of apnoea and desaturation or bradycardia sufficient to require respiratory support. Inclusion of outcomes data for these infants may have altered the findings of the trial.
Implications for practice
The data recovered in this review do not provide sufficient evidence to inform policy or practice regarding whether the nasal versus the oral route of enteral feeding tube placement is preferable for preterm or low birth weight infants. The trials do not provide evidence that the route of feeding tube placement affects feed tolerance (time to achieve full enteral feeds) or the incidence or frequency of apnoea or desaturation or bradycardia. In current practice, the decision regarding the route of tube placement seems to be based on clinician preference and local or regional precedence (Birnbaum 2009).
Implications for research
A large randomised controlled trial would be needed to determine if the use of nasally compared with orally placed feeding tubes improves feeding and growth without increasing adverse consequences in preterm or low birth weight infants. Such trials should probably focus on very low birth weight or very preterm infants since this population is more likely to be affected by respiratory compromise and other adverse events associated with feeding tube placement. Engagement with parent and family advocates is needed to inform the development of these trials and ensure that the strategies for nutrition support are consistent with the ethos of family-centred care and that the outcomes assessed are those of most importance to infants and families (POPPY Steering Group 2009; Howell 2011).
We thank Judith Hawes and Peter McEwan for contributing to the inception version of this review (Hawes 2004).
We thank Ann Dsilna for clarifying aspects of her study (Dsilna 2005).
Data and analyses
- Top of page
- Authors' conclusions
- Data and analyses
- What's new
- Contributions of authors
- Declarations of interest
- Sources of support
- Differences between protocol and review
- Index terms
Last assessed as up-to-date: 15 October 2012.
Contributions of authors
William McGuire and Julie Watson revised the protocol for this review, undertook electronic searches and handsearches, screened the title and abstract of identified studies and the full text of potentially relevant studies. The authors independently assessed the methodological quality of the included trials, extracted the relevant information and completed this final review update.
Declarations of interest
Sources of support
- NIHR Centre for Reviews and Dissemination, University of York, UK.
- 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
Differences between protocol and review
We have revised the outcomes for this review. Adverse events outcomes now include the incidence of non-intentional removal or displacement of feeding tube.
Medical Subject Headings (MeSH)
*Infant, Low Birth Weight; *Infant, Premature; Enteral Nutrition [*instrumentation; methods]; Infant, Newborn; Intubation, Gastrointestinal [*methods]; Intubation, Intratracheal [*methods]; Randomized Controlled Trials as Topic
MeSH check words