1. Objectives

To evaluate the effects of non-nutritive sucking on physiologic stability and nutrition in preterm infants

2. How studies were identified

The following databases were searched in February 2016:

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

Reference lists were also searched and the authors directly contacted researchers in the field

3. Criteria for including studies in the review

3.1 Study type

Randomized controlled trials and quasi-randomized controlled trials, excluding crossover trials

3.2 Study participants

Preterm infants born at less than <37 weeks’ postconceptional age

(Studies enrolling both term and preterm infants were excluded)

3.3 Interventions

Non-nutritive sucking involving the use of a pacifier or other method compared with no non-nutritive sucking

(Non-nutritive sucking could occur before, during or after gavage feeding by a naso/orogastric tube; before or after oral bottle- or breastfeeding; or at times not associated with feeding)

3.4 Primary outcomes

• Time taken to achieve exclusive oral feeding (all nutrient volumes taken without gavage in a 24-hour period)
• Breastfeeding at discharge
• Length of hospital stay
• Weight gain during hospital stay (grams per day)

Secondary outcomes included time spent in the neonatal intensive care unit (NICU), age of infant at full oral feeding, episodes of bradycardia during hospital stay, episodes of oxygen desaturation during hospital stay, activity or behaviour measured by a validated tool, intestinal transit time, neurodevelopmental outcomes measured by a validated tool at 12 months of age, classification of disability at 12 months of age (including auditory and visual disability), and other clinically relevant outcomes as determined by trial authors

4. Main results

4.1 Included studies

Twelve randomized controlled trials, enrolling 746 infants, were included in this review

• Data from eight trials were pooled in meta-analysis
• Mean gestational age ranged from 29 to 32.5 weeks and mean birthweight ranged from 1076 to 1651 grams
• The non-nutritive sucking intervention was a pacifier in 11 studies and a gloved finger in one trial
• Non-nutritive sucking occurred before gavage feeding in three trials; during gavage feeding in four trials; during and after gavage feeding in two trials; before bottle feeding in two trials; and was not related to feeding in two trials

4.2 Study settings

• Australia, Brazil, China, the United Kingdom of Great Britain and Northern Ireland, and the United States of America (8 trials)
• All trials took place in neonatal centres

4.3 Study settings

How the data were analysed
Non-nutritive sucking was compared with no non-nutritive sucking. 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). Heterogeneity was regarded as moderate if I²>50% and high if I²>75%. Subgroup analyses were not performed due to a paucity of data

Results
Primary outcomes
Time taken to achieve full oral feeding
Time to transition from gavage to full oral feeding was reduced by five and a half days with non-nutritive sucking in pooled analysis of two trials including 87 infants (MD -5.51 days, 95% CI [−8.20 to −2.82], I²=0%). In a further trial in 40 infants, the time to transition from gavage to bottle-feeding was reduced by two days in the intervention group (3 days versus 5 days, p=0.001). Time to transition from the start of oral feeding to full oral feeding was reduced with non-nutritive sucking during and before gavage feeding in two trials including 100 infants (MD −2.15 days, 95% CI [−3.12 to −1.17], I²=59%). In a trial involving 303 infants, no difference between treatment and control groups was found for the time from birth until full breastfeeding or receiving mother’s milk from another feeding device (MD −1.00 days, 95% CI [−6.71 to 4.71]).

Full breastfeeding at discharge
No difference between treatment and control groups was found for the proportion of infants fully breastfeeding or receiving mother’s milk from another feeding device at discharge (RR 1.08, 95% CI [0.88 to 1.33], 1 trial/303 infants). In another trial involving 40 infants, no difference was found between treatment and control groups in exclusive maternal breastfeeding on hospital discharge (p=0.41).

Length of hospital stay
Non-nutritive sucking before or during gavage feeding reduced length of hospital stay by more than four and a half days in pooled analysis of data from five trials (MD −4.59 days, 95% CI [−8.07 to −1.11], 501 infants; I²=19%).

Weight gain (grams/day)
In pooled analysis of three trials involving 103 infants, weight gain was not significantly different between treatment and control groups (MD −1.57 grams/day, 95% CI [−3.50 to 0.37], I²=0%). In a study in 60 infants employing non-nutritive sucking before gavage feeding, no difference in percentage weight gain between the treatment and control groups was reported. In a further study in 30 infants trialling non-nutritive sucking during gavage feeding, a significantly greater weight gain was found in the treatment group by the second week, with the difference remaining significant for the six-week study period.

Additional outcomes
In two trials involving 117 infants no effect of non-nutritive sucking on behavioural state was found. However, using the Anderson 12-level Behavioral State Scale, in one trial involving 24 infants it was reported that the treatment group transitioned from quiet sleep to drowsy more frequently, while the control group more often transitioned from quiet sleep to restless awake. Using the same scale, in another trial involving 42 infants it was reported that sleep states were more frequent in the treatment group, while restless states occurred twice as often in the control group. In one trial in 30 infants, intestinal transit time was reduced with non-nutritive sucking during gavage feeding (MD −10.50 hours, 95% CI [−13.74 to −7.26]). In a trial of 18 infants, gastric emptying time was not reduced with non-nutritive sucking, and in another trial of 21 infants, concentrations of motilin, gastrin, insulin, or insulin-like growth factor-1 did not differ between treatment and control groups. No statistically significant difference was found between treatment and control groups for the outcomes age at full oral feeding, episodes of bradycardia, or episodes of oxygen desaturation. No studies reported on neurodevelopmental outcomes or time spent in NICU.

5. Additional author observations*

Using GRADE criteria, the quality of evidence for all major outcomes was graded as low or very low due to factors such as being at high risk of selection bias, performance bias, detection bias, other bias due to non-adherence, or analyses demonstrating moderate heterogeneity or being based on only one study.

Time taken to transition from gavage to full oral feeding and from initiating oral feeding to full oral feeding was shortened with non-nutritive sucking interventions, and length of hospital stay and intestinal transit time were also reduced. Weight gain was not affected by non-nutritive sucking interventions and no clear effect on other outcomes was observed.

Further high-quality trials of non-nutritive sucking are needed, and long-term outcomes such as neurodevelopment should be assessed.