1. Objectives

To determine the effectiveness of oral stimulation interventions in preterm infants on attainment of full oral feeding, with regard to gestational age at birth and type of oral feeding

2. How studies were identified

The following databases were searched in 2016:

• Cochrane Neonatal Group Specialized Register
• CENTRAL (The Cochrane Library 2016, Issue 1)
• MEDLINE
• EMBASE
• CINAHL
• ClinicalTrials.gov
• WHO International Trials Registry and Platform
• ISRCTN Registry

Relevant journals and conference proceedings were also searched

3. Criteria for including studies in the review

3.1 Study type

Randomized controlled trials, including quasi-randomized trials. Crossover trials were excluded

3.2 Study participants

Premature infants born at <37 weeks’ postmenstrual age

(Studies enrolling infants of all gestational ages were included if data could be extracted for those born at <37 weeks)

(Trials enrolling infants with conditions such as neurological or structural impairments, respiratory disease, or conditions precluding oral feeding were excluded)

3.3 Interventions

Oral stimulation interventions, delivered by a trained person or parent, at any dose, timing, frequency, intensity, or duration, compared with no intervention, a non-oral intervention, or another oral stimulation intervention

3.4 Primary outcomes

• Time taken to achieve exclusive oral feeding (all nutrient volumes taken without gavage in a 24-hour period)
• Time spent in the neonatal intensive care unit (NICU)
• Length of hospital stay
• Duration of parenteral nutrition

Secondary outcomes included exclusive oral feeding at 40 weeks’ postmenstrual age, exclusive direct breastfeeding at 40 weeks’ postmenstrual age, any direct breastfeeding at 40 weeks’ postmenstrual age, weight gain, length, head circumference, maturation in sucking strength (milk intake in mL/minute, suction amplitude in mmHg/sucks/minute), developmental outcomes assessed using validated instruments at 12 to 18 months, necrotising enterocolitis (≥Bell’s Stage 2), retinopathy of prematurity, family satisfaction with the intervention, non-compliance with the intervention, and adverse outcomes such as sepsis, oral infection, oral trauma, apnoea or bradycardia episodes requiring intervention, increased salivary flow, oxygen dependence at 36 weeks’ postmenstrual age, and death during initial hospital stay

4. Main results

4.1 Included studies

Sixteen randomized controlled trials, enrolling 825 preterm infants, were included in this review

• All included trials investigated finger stimulation protocols before feeds (gavage or oral) with or without other supports: nine trials compared oral stimulation to no intervention/standard care and seven trials compared oral stimulation with a non-oral stimulation, such as stroking the infant’s body
• Nine trials used the “Fucile Protocol”: 12 minutes of structured finger stroking followed by three minutes of pacifier sucking once a day prior to feeding
• Other interventions differed in duration and frequency, with some interventions occurring five times per day

4.2 Study settings

• Brazil (3 trials), China (2 trials), France, India, Iran (2 trials), the United Kingdom of Great Britain and Northern Ireland (2 trials), and the United States of America (5 trials)

4.3 Study settings

How the data were analysed
Two comparisons were made: i) oral stimulation versus no intervention/standard care, and ii) oral stimulation versus a non-oral intervention. Fixed effect meta-analysis was used to generate risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, both with corresponding 95% confidence intervals (CI). To investigate potential sources of heterogeneity, the following subgroup analyses were planned but not conducted due to a paucity of data:

• Infants born at <28 weeks’ postmenstrual age
• Infants born at 28 to <32 weeks’ postmenstrual age
• Exclusively breastfed infants
• Exclusively bottle-fed infants
• Infants both breast- and bottle-fed

Results
Oral stimulation versus no intervention/standard care
Time taken to achieve exclusive oral feeding
In pooled analysis of eight trials involving 376 infants, the time to achieve full oral feeding was reduced by almost five days with oral stimulation in comparison with no intervention or standard care (MD -4.81 days, 95% CI [-5.56 to -4.06], I²=68%).

Weight gain
Meta-analysis of two trials including 81 infants demonstrated no significant difference between treatment and control groups in weight gain (MD 0.73 grams/kg/day, 95% CI [-1.05 to 2.51], I²=41%).

Length of hospital stay
Length of hospital stay was reduced by more than five days with an oral stimulation intervention versus no intervention in pooled analysis of five trials involving 301 infants (MD -5.26 days, 95% CI [-7.34 to -3.19], I²=61%).

Duration of parenteral nutrition
In one trial including 19 preterm infants, the duration of parenteral nutrition was reduced by more than five days in the intervention group relative to the controls (MD -5.30 days, 95% CI [-9.73 to -0.87]).

Additional outcomes
For the outcomes exclusive direct breastfeeding at discharge and any breastfeeding at discharge, results were not indicative of an effect (RR 1.83, 95% CI [0.96 to 3.48], 1 trial/59 infants, and RR 1.24, 95% CI [0.58 to 2.66], 2 trials/110 infants, respectively). No other pre-specified outcomes were reported on in the included studies.

Oral stimulation versus a non-oral intervention
Time taken to achieve exclusive oral feeding
Pooled analysis of five trials involving 256 infants demonstrated a significant reduction in time to achieve exclusive oral feeding of nine days in the treatment group (MD -9.01 days, 95% CI [-10.30 to -7.71], I²=25%).

Length of hospital stay
Length of hospital stay was reduced by almost three days in the oral stimulation intervention group (MD -2.94 days, 95% CI [-4.36 to -1.51], I²=48%, 6 trials/352 infants).

Duration of parenteral nutrition
In one trial including 98 infants, the duration of parenteral nutrition was reduced by more than eight days in the intervention group relative to the controls (MD -8.70 days, 95% CI [-15.46 to -1.94]).

Additional outcomes
For the outcome exclusive breastfeeding at discharge, no evidence of an effect of oral stimulation was found (RR 0.96, 95% CI [0.72 to 1.28], 1 trial/196 infants). No other outcomes were able to be combined in pooled analyses, and no adverse effects other than self-resolving episodes of apnoea and bradycardia were reported.

5. Additional author observations*

For the comparison oral stimulation versus no treatment/standard care, evidence for all outcomes was rated as low to very low quality using GRADE criteria. Evidence for the comparison oral stimulation versus a non-oral intervention was rated as moderate for exclusive breastfeeding at discharge, and low for all other outcomes. Downgrading for both comparisons was performed due to risk of reporting bias, detection bias, selection bias, performance bias, attrition bias, and heterogeneity. Overall, only one of the sixteen included trials was judged to be at low risk of allocation concealment bias. Given the high risk of bias for almost all included trials, the findings of this review should be interpreted with caution.

The evidence summarized in this review suggests that preterm infants who receive oral stimulation take fewer days to attain full oral feeding, have a reduced length of hospital stay, and a reduced duration of parenteral nutrition. Oral stimulation did not affect weight gain or breastfeeding at discharge.

Further adequately powered studies of high methodological quality are warranted. Such trials should clearly define the intervention, use uniform terminology to describe suck and swallow maturation, and measure clinically important long-term outcomes.