Description of the condition
Mechanical ventilation (MV) is often necessary when treating ill newborns, particularly when they are preterm. Although usually given for a short time, occasionally MV may be necessary for a long period. MV has been related to short-term complications and impaired long-term respiratory and developmental outcomes (Singer 1997; Bancalari 2001; Walsh 2005), with longer duration of MV associated with an increased risk of complications.
Description of the intervention
Different methods of respiratory support have been developed with the aim of improving the effectiveness of assisted ventilation and minimising its adverse effects, that is, high frequency ventilation, conventional ventilation (CV) with all its variants and continuous positive airway pressure (CPAP) (Cools 2009; Henderson-Smart 2009; Wheeler 2010; Brown 2011). However, it is uncertain whether the position of the infant while on MV has an impact on clinical outcome.
How the intervention might work
The main positions that can be used are supine, prone or lateral decubitus. Although it is not known which is the best way to position the newborn, there is a trend towards keeping ventilated infants in a supine position, mainly for ease of observation and handling of the infant. These patients require frequent monitoring and interventions, and they may have many catheters and tubes (including urinary, umbilical, and other vascular catheters and drainage tubes).
Why it is important to do this review
Studies performed on other types of patients suggest that the change from supine to other positions, and specifically to prone, can have some advantages. For example, several studies in adults and children on MV, mainly for acute respiratory failure (ARF) and acute respiratory distress syndrome (ARDS), showed transitory benefits of the prone position on oxygenation (Piehl 1976; Douglas 1977; Fridrich 1996; Chatte 1997; Curley 2000; Gattinoni 2001; Gattinoni 2010). Other studies in newborn infants not needing assisted ventilation found some benefit of positions other than the traditional supine position, especially the prone position. Observed benefits were improvements in oxygenation (Schwartz 1975; Martin 1979; Kishan 1981) and in other functional respiratory parameters (Masterson 1987; Wolfson 1992; Fox 1993; Adams 1994; Itakura 1998). It has been suggested that non-supine positions could have additional benefits regarding feeding, gastric emptying and suctioning (Yu 1975; Hewitt 1976; Mizuno 2000) and on some aspects of development during the first months of life (Jantz 1997; Davis 1998; Dewey 1998; Visscher 1998; Ratliff-Schaub 2001). In addition, postural changes could contribute to preventing motor abnormalities.
These interventions are easy to perform and have virtually no economic cost. In light of these results, it is of great interest to know whether placing infants in positions other than supine during MV could be of any clinical benefit.
- to assess the effects of different positioning of newborn infants receiving MV (supine versus lateral decubitus or prone) on improving short-term respiratory outcomes.
- to assess the effects of different positioning of newborn infants receiving MV on mortality, neuromotor and developmental outcomes in the long-term and other complications of prematurity.
Criteria for considering studies for this review
Types of studies
Randomised or quasi-randomised trials.
Types of participants
Term or preterm neonates requiring any type of positive pressure MV including CPAP.
Types of interventions
Placing infants in a supine position compared with placing them in a prone or lateral decubitus position or undertaking a strategy of regular position change.
Types of outcome measures
- Oxygenation during MV, measured by arterial oxygen tension (PO
2), transcutaneous method (tcPO 2) or haemoglobin oxygen saturation.
- Decrease in characteristics of ventilator: peak inspiratory pressure or mean airway pressure (cm H
2O) and fraction of inspiratory oxygen.
- Short-term pulmonary complications: pneumothorax or pulmonary interstitial emphysema (PIE).
- Duration of ventilator support.
- Bronchopulmonary dysplasia (BPD) or chronic lung disease (CLD) either at 28 days after birth or 36 weeks' postmenstrual age, respectively.
- Changes in carbon dioxide tension (PCO
- Changes on pulmonary mechanics.
- Short-term complications (accidental extubation; dislodgement of central catheters, urinary or drainage tubes).
- Peri- or intraventricular haemorrhage.
- Gastrointestinal or feeding problems: necrotizing enterocolitis (NEC) or intolerance of enteral feeding.
- Days of stay in neonatal intensive care unit (NICU).
- Days of stay in hospital.
- Neonatal mortality (death during the first 28 days of life).
- Infant mortality (death during the first year of life).
- Long-term neurodevelopmental outcomes at age two years: rates of cerebral palsy as assessed by physician, developmental delay (i.e., IQ < 2 standard deviations) on validated assessment tools (e.g., the Stanford-Binet Intelligence Scale or others) or sensory impairment.
- Cutaneous and joint problems, i.e., dependent oedema, pressure ulcers of the skin, joint contractures or ankylosis.
Search methods for identification of studies
We identified randomised controlled trials (RCTs) and systematic reviews by electronically searching the following databases:
• CENTRAL (The Cochrane Library 2012, Issue 3);
• MEDLINE (from May 2006 to December 2012);
• EMBASE (from May 2006 to December 2012);
• CINAHL (from May 2006 to December 2012);
• Oxford Database of Perinatal Trials.
Unpublished studies were identified by handsearching conference proceedings of the Society for Pediatric Research from May 2006 to July 2011. The search strategy developed by the Cochrane Neonatal Review Group was followed, using free text words and MeSH headings (Furlan 2009). No language restrictions were set. A search was not conducted for studies published before May 2006 because they were included in the previous Cochrane review (see description in the Appendices).
The standard search strategy of the Cochrane Neonatal Review Group, as outlined in The Cochrane Library, was used and combined with the following MeSH search terms: "Posture", "Prone Position", "Ventilators, Mechanical", "Respiration, Artificial", "Positive-Pressure Respiration", "Infant, Newborn". The following text words were also used: "infant positioning" (tw), "patient positioning" (tw), "body position" (tw), "prone" (tw), "lateral decubitus" (tw), "mechanical ventilation" (tw), "neonate" (tw) and "premature" (tw).
See: Cochrane Neonatal Group methods used in reviews.
We also searched the ClinicalTrials.gov (http://www.clinicaltrials.gov) web site.
Data collection and analysis
Selection of studies
Three review authors independently and unblinded assessed the trials for inclusion in the review without prior consideration of their results. We resolved disagreements on inclusion through discussion between the review authors. Excluded studies are listed in the table 'Characteristics of excluded studies' including the reasons for their exclusion. We only evaluated full papers. We did not apply language restrictions.
We identified twenty-one trials. Ten of them failed to met the inclusion criteria (Wagaman 1979; Baird 1991; Schrod 1993; McEvoy 1997; Itakura 1998; Curley 2005 (and Fineman 2006, multicentre); Ibrahim 2007; Ancora 2009; Zhu 2010). The reasons for exclusions are listed in the table 'Characteristics of excluded studies'. Twelve trials were included (Heaf 1983; Bozynski 1988; Crane 1990; Fox 1990; Mendoza 1991; Bjornson 1992; Schlessel 1993; Mizuno 1995; Mizuno 1999; Chang 2002; Antunes 2003; Aly 2008). Nine studies were randomised cross-over controlled trials whereas Schlessel 1993, Antunes 2003 and Aly 2008 were randomised parallel group controlled trial. One of the included studies was not evaluated in the previous review.
Data extraction and management
The following data were extracted: study design (RCT), study characteristics (e.g., recruitment modality, source of funding, risk of bias), patient characteristics (e.g., number of participants, age, gender), description of the experimental and control interventions, co-interventions, duration of follow-up, types of outcomes assessed, and the authors’ results and conclusions. All review authors extracted the data independently using prepared data extraction forms. We resolved discrepancies by discussion between all the review authors. We contacted authors of individual trials for missing information and clarification of published data, when necessary. We extracted data from graphs, if necessary (Bozynski 1988; Bjornson 1992). We summarized key findings in a narrative format.
Assessment of risk of bias in included studies
We used the standard methods of the Cochrane Neonatal Review Group and the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). In particular, this included analysis of randomised crossover trials. The methodological quality of each trial was reviewed independently by the review authors. The review authors independently assessed the risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions, detailed below.
(1) Random sequence generation (checking for possible selection bias)
For each included study, we assessed whether the method used to generate the allocation sequence was described in sufficient detail to allow an assessment of whether it should produce comparable groups. We assessed the methods as:
• low risk (any truly random process, e.g., random number table, computer random number generator);
• high risk (any non-random process, e.g., odd or even date of birth, hospital or clinic record number); or
• unclear risk.
(2) Allocation concealment (checking for possible selection bias)
For each included study, we assessed whether the method used to conceal the allocation sequence was described in sufficient detail and determined whether intervention allocation could have been foreseen in advance of or during recruitment, or changed after assignment. We assessed the methods as:
• low risk of bias (e.g., telephone or central randomisation, consecutively numbered sealed opaque envelopes);
• high risk of bias (open random allocation, unsealed or non-opaque envelopes, alternation, date of birth);
• unclear risk of bias.
(3) Blinding of participants, personnel and outcome assessment (checking for possible performance bias and detection bias)
We described for each included study the methods used, if any, to blind study participants and personnel from knowledge of which intervention a participant received and to blind outcome assessors from knowledge of which intervention a participant received. We considered that studies were at low risk of bias if they were blinded, or if we judged that the lack of blinding would be unlikely to affect results. We assessed blinding separately for different outcomes or classes of outcomes.
We assessed the methods as:
• low, high or unclear risk of bias for participants;
• low, high or unclear risk of bias for personnel.
(4) Incomplete outcome data (checking for possible attrition bias due to the amount, nature and handling of incomplete outcome data)
We described for each included study, and for each outcome or class of outcomes, the completeness of data including attrition and exclusions from the analysis. We stated whether attrition and exclusions were reported and the numbers included in the analysis at each stage (compared with the total randomised participants), whether reasons for attrition or exclusion were reported, and whether missing data were balanced across groups or were related to outcomes.
We would re-include missing data in the analyses which we undertook where sufficient information was reported or could be supplied by the trial authors.
We assessed methods as:
• low risk of bias (e.g., no missing outcome data, missing outcome data balanced across groups);
• high risk of bias (e.g., numbers or reasons for missing data imbalanced across groups, ‘as treated’ analysis done with substantial departure of intervention received from that assigned at randomisation);
• unclear risk of bias.
(5) Selective outcome reporting (checking for reporting bias)
We described for each included study how we investigated the possibility of selective outcome reporting bias and what we found.
We assessed the methods as:
• low risk of bias (where it was clear that all of the study’s pre-specified outcomes and all expected outcomes of interest to the review had been reported);
• high risk of bias (where not all the study’s pre-specified outcomes had been reported, one or more of the reported primary outcomes were not pre-specified, outcomes of interest were reported incompletely and so could not be used, study failed to include results of a key outcome that would have been expected to have been reported);
• unclear risk of bias.
(6) Other sources of bias (checking for bias due to problems not covered by one to five above)
We described for each included study any important concerns we had about other possible sources of bias.
We assessed whether each study was free of other problems that could put it at risk of bias:
• low risk of other bias;
• high risk of other bias;
• unclear whether there was risk of other bias.
(7) Overall risk of bias
We made explicit judgements about whether studies were at high risk of bias according to the criteria given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). With reference to (1) to (6) above, we assessed the likely magnitude and direction of the bias and whether we considered it was likely to impact on the findings.
Measures of treatment effect
For continuous variables, one of the studies (Fox 1990) provided individual data for the partial pressure of oxygen (PaO
For the dichotomous variable desaturation episodes, estimating the degree of correlation meant to estimate the number of patients presenting with the outcome of interest under both treatments. Since only one crossover trial reported this outcome (Chang 2002), present in as few as five cases in one of the treatment groups, we compared the results assuming the lowest possible correlation between treatments (no patients desaturated under both treatments) and assuming the highest correlation (five patients desaturated under both treatments). Since the results didn't differ, it was irrelevant which assumption to make.
Unit of analysis issues
Analysis of those studies with a crossover design was conducted using paired data according to the methodology outlined in Elbourne 2002. The statistical method took into account the correlation existing between repeated observations of the patients, and thus allowed the computation of adjusted standard deviations for the effect sizes (differences in means for continuous variables and odds ratios for dichotomous variables). A necessary imputation of the method was the degree of existing correlation between repeated measures.
Assessment of heterogeneity
We assessed presence of heterogeneity by means of the I
Assessment of reporting biases
Two review authors independently assessed each included study for possible reporting biases. We were unable to investigate reporting biases using funnel plots as there were fewer than 10 studies included in the analyses.
The adjusted effect sizes computed for crossover trials, and the usual effect sizes computed for parallel trials were combined by means of the inverse variance method using a random-effects model.
Subgroup analysis and investigation of heterogeneity
We planned subgroup analyses on the basis of:
- gestational age (or birth weight): 37 or more completed weeks and less than 37 weeks;
- birth weight: < 1500 g and > 1500 g;
- type of ventilatory support: continuous ventilation (CV), synchronized intermittent mandatory ventilation (SIMV), high frequency oscillation ventilation (HFOV), high frequency jet ventilation (HFJV), and CPAP.
We planned to carry out sensitivity analyses to explore the effects of adequacy of allocation concealment and other risk of bias components, but there were insufficient data to do this.
Description of studies
Results of the search
We identified 21 trials. Ten of them failed to meet the inclusion criteria (Wagaman 1979; Baird 1991; Schrod 1993; McEvoy 1997; Itakura 1998; Curley 2005 (and Fineman 2006, multicentre); Ibrahim 2007; Ancora 2009; Zhu 2010). The reasons for exclusions are listed in the table 'Characteristics of excluded studies'. Twelve trials were included (Heaf 1983; Bozynski 1988; Crane 1990; Fox 1990; Mendoza 1991; Bjornson 1992; Schlessel 1993; Mizuno 1995; Mizuno 1999; Chang 2002; Antunes 2003; Aly 2008). Nine studies were randomised crossover controlled trials whereas Schlessel 1993, Antunes 2003 and Aly 2008 were randomised parallel group controlled trials. One of the included studies was not evaluated in the previous review.
A search of the online register of clinical trials www.clinicaltrials.gov did not reveal any study meeting the inclusion criteria.
Twelve trials were included (Heaf 1983; Bozynski 1988; Crane 1990; Fox 1990; Mendoza 1991; Bjornson 1992; Schlessel 1993; Mizuno 1995; Mizuno 1999; Chang 2002; Antunes 2003; Aly 2008). See table: Characteristics of included studies.
Types of infants
Term or preterm neonates requiring any type of positive pressure MV including CPAP were included. Most trials included preterm infants with gestational age ranging from 23 to 39 weeks. One study did not report the gestational age at birth (Heaf 1983) but when the reported birth weight of study infants was inspected, it was considered that, on average, the included patients were born at term. Important variations in age of the neonates were found across the studies. In six studies patients were less than one week of age (Heaf 1983; Crane 1990; Fox 1990; Schlessel 1993; Chang 2002; Aly 2008), ranging between 22 hours and seven days. In the other six trials neonates were between two and 138 days old.
All the studies enrolled preterm infants receiving MV. Infants were ventilated with intermittent MV (IMV) in 10 trials (Bozynski 1988; Crane 1990; Mendoza 1991; Bjornson 1992; Schlessel 1993; Mizuno 1995; Mizuno 1999; Chang 2002; Antunes 2003; Aly 2008). Two studies (Heaf 1983; Fox 1990) included patients on IMV and patients on CPAP. Infants were on mechanical ventilation due to RDS in six studies (Crane 1990; Fox 1990; Mendoza 1991; Bjornson 1992; Schlessel 1993; Chang 2002 in 20 out of 28 cases). In three studies patients were in a stable condition and ventilated due to CLD (Bozynski 1988; Mizuno 1995; Mizuno 1999) and in one (Antunes 2003) patients were on IMV because of prematurity (presumably due to RDS) and entered in the study at the beginning of the weaning process. In one trial ventilation was due to unilateral lung disease (three congenital diaphragmatic hernia and one with hypoplastic right lung) (Heaf 1983). No other associated conditions were defined in other trials but Bjornson 1992 described two patients with sepsis and one with patent ductus arteriosus.
Patient inclusion and exclusion criteria were not always well defined in the included studies. A variety of exclusion criteria were applied: presence of known congenital defects (Bjornson 1992; Chang 2002; Antunes 2003; Aly 2008), infants treated with sedative or paralysing drugs (Fox 1990; Chang 2002) or infants with asymmetric lung disease (Bozynski 1988; Schlessel 1993).
In five trials, simultaneous treatments during the studies were not described (Crane 1990; Fox 1990; Schlessel 1993; Mizuno 1995; Mizuno 1999). In the study by Bjornson 1992, one infant received sedation, another corticosteroids and two patients received treatment for sepsis (one of them underwent a surgical ligation of a patent ductus arteriosus). Eighteen infants received surfactant in the study of Chang 2002. In the study by Bozynski 1988, 12 newborns received furosemide and seven infants spironolactone plus thiazide diuretics. Three infants were operated on for congenital diaphragmatic hernia in the study by Heaf 1983. In the trial by Mendoza 1991 all patients received theophylline, and in the trial by Aly 2008 all patients received an antibiotic until sepsis could be ruled out.
Types of interventions
The interventions were: placing infants in a supine position compared with placing them in a prone or lateral decubitus position or undertaking a strategy of regular position change. Studies that also evaluated concomitant therapeutic interventions were excluded if the effect of the infant positioning could not be assessed independently of the second intervention’s effect.
The age and the clinical status of those infants receiving MV with different positioning were different among the 12 included trials. All the trials but one (Antunes 2003) tested positions for short periods of time, ranging from two minutes in Crane 1990 to two hours in Chang 2002. In the Antunes 2003 study, the position tested was the same from the start of MV weaning until extubation, except for three hours a day in the newborns allocated to the prone position. Aly 2008 maintained the position at all times in the supine group and changed position from one side to the other every two hours in the lateral group. In the majority of papers it was specified (or the review authors deduced) that patients were fasting. In only three studies (Mizuno 1995; Mizuno 1999; Aly 2008) was it clear that enteral nutrition was used.
Several position changes were studied: eight trials analysed short-term respiratory outcomes placing infants in a supine position compared with placing them in a prone position (Crane 1990; Fox 1990; Mendoza 1991; Bjornson 1992; Mizuno 1995; Mizuno 1999; Chang 2002; Antunes 2003). Bjornson and Crane also analysed changes between the prone and lateral right positions and supine versus lateral right position. Bozynski 1988 analysed changes between supine versus lateral right, supine versus lateral left and lateral right versus lateral left position. Aly 2008 analysed changes between the supine versus lateral alternant position. Schlessel 1993 analysed the lateral left versus lateral right position in spite of using a sequence of positions including the supine, but this latter position was not randomised. Heaf 1983 analysed the impact of position in patients with unilateral lung disease, comparing the good lung dependent versus the good lung uppermost.
Overall, there was a lack of consistency in the types of outcome measures reported by the trialists, and a lack of consistency in the way data were reported. Oxygenation while on MV was measured by arterial oxygen tension (Fox 1990; Schlessel 1993), transcutaneous method (Heaf 1983; Bozynski 1988) or haemoglobin oxygen saturation using pulse oximetry (Bjornson 1992; Mizuno 1995; Mizuno 1999; Chang 2002; Antunes 2003). Mendoza 1991 measured the oxygen saturation of haemoglobin by pulse oximetry, but the data were not useable due to deficiencies in data reporting (mean point estimate without measure of standard deviation). Carbon dioxide (CO2) tension was measured by a transcutaneous monitor (Heaf 1983; Bozynski 1988; Crane 1990; Mizuno 1995; Mizuno 1999) or by arterial samples (Schlessel 1993; Aly 2008). Some papers measured different physiological pulmonary parameters. Tidal volume (spontaneous breath) in mL/kg and minute ventilation in mL/kg/min were measured by Mendoza 1991, Mizuno 1995 and Mizuno 1999. Schlessel 1993 measured only tidal volume but included other respiratory outcomes not used in this review (dynamic lung compliance, total pulmonary resistance, inspiratory pulmonary resistance and expiratory pulmonary resistance). Further characteristics of the trials are reported in the table Characteristics of included studies.
As most of the trials had a crossover design we could not obtain data to assess the effects of different positioning of newborn infants for receiving MV on mortality, neuromotor and developmental outcomes in the long term and other complications of prematurity. Long-term follow-up is not relevant for crossover trials; by the nature of their design, crossover trials can only address short-term effects during treatment.
We excluded ten studies; of these, in seven studies (Wagaman 1979; Baird 1991; Schrod 1993; McEvoy 1997; Itakura 1998; Ancora 2009; Zhu 2010) assignment was neither random nor quasi-random for the position. See table 'Characteristics of excluded studies'.
Risk of bias in included studies
Details of the methodological quality of each trial are given in the table 'Characteristics of included studies', Figure 1 and Figure 2. Nine studies were randomised crossover controlled trials, whereas Schlessel 1993, Antunes 2003 and Aly 2008 were randomised parallel group controlled trials.
|Figure 1. Risk of bias summary: review authors' judgements about each risk of bias item for each included study.|
|Figure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.|
Adequate sequence generation was reported by three studies (Fox 1990; Chang 2002; Antunes 2003). None of the studies used quasi-random methods of patient allocation: none alternately allocated infants to groups. The method of allocation was usually not stated, being described only by Chang 2002 (randomisation in blocks by a third person to ensure balanced combinations of positions and finally using an identification number in a sealed envelope), Fox 1990 (coin toss) and Antunes 2003 (drawing lots in the form of sealed envelopes). Only in these three studies could the allocation concealment be considered adequate.
Due to the nature of the trials, blinding of the intervention was not possible in any of the studies. The assessment of outcome measurements was not blinded in any of the studies.
Incomplete outcome data
Six studies had complete follow-up of enrolled infants (Heaf 1983; Bozynski 1988; Fox 1990; Schlessel 1993; Mizuno 1995; Mizuno 1999). In the study by Antunes 2003, one patient did not complete the protocol for unknown reasons. In the study by Bjornson 1992, two infants needed changes in the ventilatory parameters during the study and could not complete the nine sessions prescribed. In the study by Chang 2002, 10 patients (four in prone, six in supine position) did not complete the two hour protocol in the same position because of the need for interventions (airway suctioning, etc), in which case a time of equal duration was selected for comparison. Five infants were discarded in the study by Crane 1990 because of excessive transcutaneous (tc) PCO
No study pre-specified primary outcomes so it was unclear if they were free from selective reporting bias.
Other potential sources of bias
No studies had clear pre-specified methods, including a sample size calculation, and so it was clear the studies were likely to be free from other types of bias such as multiple interim analyses or premature stopping. It was considered that some studies had a particular risk of bias: in five of them co-interventions during the studies were not described (Fox 1990; Crane 1990; Schlessel 1993; Mizuno 1995; Mizuno 1999) and blinding of the intervention was not possible in any of them.
Effects of interventions
Prone versus supine (Comparison 1)
Results for PO
In another study on newborns in the weaning process (Antunes 2003) no differences were found in the SpO
Two studies (Chang 2002; Antunes 2003) quantified the number of desaturation episodes (DeSat). Both found a lower incidence of DeSat in the prone position. Both studies defined and quantified DeSat differently. Antunes 2003 defined DeSat as the detection of two episodes of Sp0
Three studies provided data for PCO
Pulmonary mechanics were assessed by means of the tidal volume and minute ventilation in three studies (Mendoza 1991; Mizuno 1995; Mizuno 1999). Results were heterogeneous for both outcomes (P = 0.009 and P = 0.044) and the meta-analysis found no evidence of effect (MD for tidal volume 0.70 mL/kg, 95% CI -0.81 to 2.2; MD for minute ventilation 19.80 mL/kg/min, 95% CI -40.54 to 80.14).
The aforementioned study by Antunes 2003 found no differences in the duration of the process of weaning between the prone and supine positions. However, once the patients had been extubated and placed in the supine position under CPAP, it was found that those who had been weaned in the supine position needed to be re-intubated during the first 48 hours more often than those who had been weaned in the prone position (7 versus 1, P = 0.049).
Prone versus lateral (Comparison 2)
Two studies provided data comparing the prone and the lateral positions. Crane 1990 assessed the effect on PCO
Lateral versus supine (Comparison 3)
Three trials compared the lateral position versus the supine: Crane 1990 and Bjornson 1992 focused on the right lateral position, Bozynski 1988 focused on both side positions. Neither the lateral right position nor lateral left position showed significant differences compared with the supine position for any of the outcomes (haemoglobin oxygen saturation, oxygen pressure (PO
Lateral right versus lateral left (Comparison 4)
One parallel clinical trial (Schlessel 1993) and one crossover trial (Bozynski 1988) provided data for this comparison. Neither showed significant effects on any outcome (PO
Good lung dependent versus good lung uppermost (Comparison 5)
One small crossover trial (Heaf 1983) provided data for this comparison and it found no significant differences in oxygen or pCO
For all position contrasts, the effects of position on other outcomes defined a priori, including clinically important outcomes, could not be assessed because of lack of data. Planned subgroup analyses could not be performed because of the lack of data.
Summary of main results
There is no evidence from these studies that any specific body position is more effective than another in producing long-term clinically relevant benefits. However, neonates on MV who were habitually in the supine position improved their oxygenation when they changed to the prone position. It cannot be concluded from these studies whether the improvement in oxygenation was due to the fact that the prone position is better or whether it is mainly due to the change in position. This improvement in oxygenation lasted only for the short time they were in the prone position. A total of 12 trials studying different positions were included, the prone versus supine, prone versus lateral right, lateral right versus supine, lateral left versus supine, lateral (alternating sides) versus supine, lateral right versus lateral left and good lung dependent versus good lung uppermost. The most robust comparison was the effect of the prone versus supine position on oxygenation outcomes, with a total of five studies providing useful data.
Relatively few small studies, quite typically with a high risk of bias (RoB), evaluated the latter comparisons thus these studies have a high likelihood of a type II error stemming from the low power of the study to detect a statistically significant and clinically relevant effect. However, studies with a high RoB typically overestimate the effect compared to studies with a low RoB.
Strengths and limitations
The primary limitation, which is common to many systematic reviews, is the lack of studies with a low RoB. Despite the fact that the majority of the studies included in this review were published in the two previous decades, methodologically well conducted studies remain scarce. Strengths of this review include the meta-analyses, which allowed us to find some significant outcome results. Considering that any change of position over the standard supine position may promote a more flexed position (similar to the fetal position) that could positively affect the outcomes, most included studies specified that both the standard position and the comparison position promoted flexion using soft cloth rolls, etc.
Nonetheless, the included studies in this review have several limitations. One limitation is related to the small sample sizes, which added up to only 224 infants for the review. Firm conclusions could not be drawn because of this limitation as well as variations in the interventions and outcomes assessed, resulting in multiple subgroups each including small numbers of patients.
Furthermore, the use of a crossover design in all the studies except three (Schlessel 1993; Antunes 2003; Aly 2008) removes the ability to measure effects on long-term outcomes. Because these three studies did not undertake a prolonged follow-up, it was not possible to determine whether the positioning might have important long-term effects.
Overall completeness and applicability of evidence
For the prone position versus supine compared to the standard supine position, the prone position was shown to be effective in improving oxygenation over short periods of time.
The magnitude of improvement in oxygenation could not be reliably established because the five eligible trials (Fox 1990; Bjornson 1992; Mizuno 1995; Mizuno 1999; Chang 2002) included a total of only 70 babies and used two different measures of oxygenation. Oxygenation in the prone position was superior in the four studies that measured oxygenation by pulse oximetry. Although there was heterogeneity across studies in the magnitude of effect, an increase in haemoglobin oxygen saturation in the prone position was shown, with a 95% confidence interval of 1.18% to 4.36%. The only study that measured PO
It is not possible to conclude whether the observed improvements in oxygenation in the prone position would be maintained over the long term. The time of exposure to the prone position in each patient was relatively short, varying from 15 minutes to two hours. It also cannot be concluded whether this benefit may be sustained after the intervention has been stopped.
It is possible that benefits of the prone position on oxygenation may have been underestimated considering that three out of five studies (Mizuno 1995; Mizuno 1999; Chang 2002) were conducted in relatively stable patients with respiratory insufficiency. Furthermore, one of the studies (Bjornson 1992) excluded some common conditions such as congenital defects and intraventricular haemorrhages.
One study (Chang 2002) assessed additional secondary outcomes such as motor activity and the number, intensity and duration of episodes of desaturation. This study found that, compared to the supine position, the prone position produced fewer episodes of desaturation and lesser levels of activity. It also found that 74% of the episodes of desaturation were associated with vigorous motor activity and crying. The study concluded that the prone position offered indirect benefits by achieving less agitation in the infants. Furthermore, this study found that improvement in oxygenation was higher in the subgroup of patients previously treated with surfactant. Another study undertaken on preterm infants on MV in the weaning phase (Antunes 2003) also found that the prone position was better than the supine position as far as desaturation episodes were concerned. The meta-analysis showed that fewer patients experience desaturation episodes in the prone position. Antunes also found that preterm infants who had been weaned in the prone position had to be re-intubated less frequently than those that had been weaned in the supine position.
The two studies of Mizuno (Mizuno 1995; Mizuno 1999) raised questions about effects that enteral feeding may have on respiratory outcomes. Although both studies offered data that suggested that the prone position may improve oxygenation during and after feeding, these data were not included in our review because all the other studies that were included were conducted during fasting periods (pre-feeding) of at least a few hours.
Only three studies including 27 patients provided data on the effect of the prone position on pC0
Several studies measured different pulmonary mechanics parameters. These outcomes were included in a meta-analysis only when studies using comparable measures were available. Only tidal volume and minute ventilation during spontaneous breathing could be analysed. Significant differences between the prone and supine positions were not found. Nonetheless, considering the small numbers that were analysed, it cannot be excluded that small effects on these parameters may exist or that effects on pulmonary mechanics due to changes in position might be better reflected by other parameters.
Only one study (Bjornson 1992) assessed the effect of the prone position versus lateral position on haemoglobin oxygen saturation and found a slight improvement in the prone position (MD 2.13 mm Hg, 95% CI 0.33 to 3.93).
One trial (Heaf 1983) compared blood gases in patients with asymmetric respiratory pathology who were positioned with their good lung dependent versus the good lung uppermost. There were no significant differences between the positions in p0
Complications associated with interventions
None of the trials reported complications or undesirable effects attributable to the change in positioning. Complications are referred to in a generic way, and in most of the trials complications were not explicitly mentioned in the objectives.
Immediate accidents such as accidental extubation, bleeding, airway loss, etc are manipulative problems that may be observed in general clinical practice even though they weren't observed in controlled settings of clinical trials with fairly stable patients.
Quality of the evidence
The methodological quality of most of the included studies was good suggesting that the data were valid, but it was not possible to mask caregivers to the nature of the intervention, although blinding of some outcome assessments could have been possible. The lack of blinding may have resulted in surveillance and ascertainment biases.
Agreements and disagreements with other studies or reviews
Ostensibly these results are consistent with the previous review, which concluded that there is evidence that the prone position is neither superior nor inferior for neonates with ventilator support. In comparison to the previous review, three included studies are new and two have a low RoB; therefore our findings are thought to be more robust.
Implications for practice
Evidence from randomised controlled trials indicates that, compared to the supine position, the prone position improves oxygenation, including desaturation episodes, when used for short periods of time or when patients were stable and in the weaning process. We found no evidence about whether or not the prone position produces sustained benefits on pulmonary or other parameters.
Although adverse effects from the prone position were not observed in the studies reviewed, they cannot be disregarded with confidence. The effect of position has generally been tested under highly controlled circumstances in stable patients. Therefore, use of the prone position should be carefully monitored, particularly to avoid damage to the tracheal tube or central catheters during manipulation of the neonate.
Implications for research
Large controlled clinical trials comparing the prone position against the supine position should be conducted. Controlled trials with a parallel design could assess not only short-term outcomes but also long- and medium-term outcomes such as mortality, duration of ventilator support and hospitalisation, cutaneous and joint problems and neurodevelopment. The conduct of large studies among less selected patients (including those who are less stable) may help to verify whether the intervention benefits newborns with different diseases or disease severity and whether subgroups of responsive patients may be identified.
It is difficult to design a pragmatic trial that ensures that caregivers, parents and investigators are unaware of the allocated intervention of position. This lack of blinding may cause surveillance and ascertainment biases.
Questions concerning the effects of lateral positions still need answers. Likewise, studies that assess the lateral decubitus position with the good lung dependent versus good lung uppermost in patients with asymmetrical respiratory pathology should be conducted.
To Pharmacia Laboratories for help in searching the EMBASE database for the first edition of this review.
The work of Ms Roqué in the first edition of this review was partly funded by grant 01/A060 of the Instituto de Salud Carlos III, Subdirección General de Investigación Sanitaria.
Data and analyses
- Top of page
- Authors' conclusions
- Data and analyses
- What's new
- Contributions of authors
- Declarations of interest
- Sources of support
- Index terms
Last assessed as up-to-date: 15 December 2012.
Protocol first published: Issue 2, 2002
Review first published: Issue 2, 2003
Contributions of authors
In the original and 2006 version of the review:
Albert Balaguer and Joaquin Escribano wrote the protocol.
Albert Balaguer and Joaquin Escribano searched the literature, independently reviewed all possible trials for inclusion, extracted details of the studies’ methods and results, wrote the initial synthesis of the results.
Marta Roqué reviewed all possible trials for inclusion, performed the statistical analysis and entered the data into RevMan, contributed to the synthesis of the results.
All three review authors contributed to and agreed with the final versions.
In the present revision of this review:
Albert Balaguer and May Rivas-Fernandez independently selected new trials for inclusion from initial searches.
May Rivas-Fernandez updated the ’Risk of bias’ tables for trials already included in the review and similarly for any new trials identified in the update which was checked by Albert Balaguer and Marta Roqué.
Albert Balaguer and May Rivas-Fernandez updated the results section and this was checked by Marta Roqué and Joaquín Escribano.
All the review authors participated in the restructuring of the remaining areas of the review and read and agreed with this updated review.
Declarations of interest
Sources of support
- Hospital Universitari St Joan Reus, Spain.
- Universitat Rovira i Virgili, Spain.
- Abbot Laboratories, Spain.
- Instituto de Salud Carlos III. Subdirección General de Investigación Sanitaria, (01/A060), Spain.
- 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
Medical Subject Headings (MeSH)
MeSH check words