1. Objectives

To evaluate cup feeding versus other forms of supplemental enteral feeding on weight gain and achievement of successful breastfeeding in newborn infants unable to fully breastfeed

2. How studies were identified

The standard search strategy for the Cochrane Neonatal Review Group was used and the following databases were searched to January 2016:

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

In addition, relevant conference proceedings were searched

3. Criteria for including studies in the review

3.1 Study type

Randomized or quasi-randomized controlled trials. Crossover trials were excluded

3.2 Study participants

Preterm and term infants up to 44 weeks’ postmenstrual age or 28 days’ postnatal age who were unable to fully breastfeed

3.3 Interventions

Oral feeding of either expressed breast milk or a combination of expressed breast milk and formula by a cup versus other types of supplemental enteral feeding, including bottle feeding and gastric tube feeding

(A cup or something of similar design was to be used for supplemental feeding in the intervention group to ensure that the infant lapped the milk)

3.4 Primary outcomes

• Weight gain (g/kg/day)
• Time to full breastfeeding with acceptable weight gain (15 to 30 g/day)
• Proportion not breastfeeding at hospital discharge, and at three and six months of age
• Proportion not fully breastfeeding at hospital discharge, and at three and six months of age

Secondary outcomes included: mean feed times; number of choking events, aspiration events, infection events, physiological instability events (i.e., bradycardia, apnoea, low oxygen saturations); gestational age at discharge; length of hospital stay; cost; parental satisfaction and anxiety; neurodevelopmental outcomes at 18 and 24 months of age; and death

4. Main results

4.1 Included studies

Five randomized controlled trials, enrolling 971 preterm infants, were included in this review:

• All studies enrolled preterm infants with mean gestational ages of 29 to 35 weeks whose mothers indicated that they intended to breastfeed
• All studies compared cup versus bottle feeds as a supplement to breastfeeding when transitioning from full nasogastric tube feeds to full breast feeds
• Supplemental feeds were initiated when healthcare personnel deemed the infants ready or when the infants met a specified age or weight criteria
• In one trial, infants were randomized by three weight strata: 500 g to 999 g, 1000 g to 1499 g, and 1500 g to 1699 g. All infants in this trial were fed by nasogastric tube until they weighed 1600 g, after which time breastfeeding was encouraged
• In one trial, data were not reported for those infants who developed a disease that prevented oral feeding for longer than two days or who received non-compliant supplemental feeds (85 of 607 infants enrolled)

4.2 Study settings

• Australia, Brazil, Turkey, and the United Kingdom of Great Britain and Northern Ireland (2 trials)
• Three trials were single-centre trials conducted in a hospital setting, one trial was carried out across two tertiary hospitals and 54 peripheral hospitals, and one trial was conducted in three different hospitals

4.3 Study settings

How the data were analysed
Supplemental feeding with cups was compared to supplemental feeding with bottles. Fixed-effects models were used for meta-analysis and heterogeneity was investigated using the I² statistic. For continuous outcomes, mean differences (MD) and 95% confidence intervals (CI) were generated, and for dichotomous outcomes, relative risks (RR) and 95% CI were produced. Sensitivity analyses excluding trials at risk of bias were planned but not conducted due to a paucity of data. To investigate potential sources of heterogeneity, the following subgroup analyses were planned:

• Gestational age: preterm (<37 weeks’ gestation) versus term (≥37 weeks’ gestation)
• Oral-facial abnormalities (e.g., cleft lip or palate): present versus absent

Results
Supplemental feeding using cup versus bottle
Weight gain
In one trial including 78 infants, no statistically significant difference between intervention and control groups was found for the outcome weight gain per kg per day (MD -0.60 g/kg/day, 95% CI [-3.21 to 2.01]). Weight gain in the first seven days of the study was reported in a further trial including 522 infants in which no difference was found between intervention and control groups (MD -0.10 g/day, 95% CI [-0.36 to 0.16]).

Proportion not breastfeeding at hospital discharge
Meta-analysis showed a statistically significant 36% decrease in the risk of infants not breastfeeding at discharge with supplemental cup feeding in comparison to supplemental bottle feeding (RR 0.64, 95% CI [0.49 to 0.85], p=0.0016; I²=72%; 4 trials/957 infants).

Proportion not breastfeeding at three months of age
Pooled analysis demonstrated a statistically significant 17% decrease in the risk of infants not breastfeeding at three months of age with supplemental cup feeding (RR 0.83, 95% CI [0.71 to 0.97], p=0.018; I²=0%; 3 trials/883 infants).

Proportion not breastfeeding at six months of age
The risk of not breastfeeding at six months of age was reduced by 17% among infants receiving supplemental feeds via cups (RR 0.83, 95% CI [0.72 to 0.95]; p=0.0055; I²=55%; 2 trials/703 infants).

Proportion not fully breastfeeding at hospital discharge
Pooled results demonstrated a statistically significant 39% decrease in the risk of infants not fully breastfeeding at hospital discharge among those receiving supplemental cup feeds (RR 0.61, 95% CI [0.52 to 0.71], p<0.00001; I²=57%; 4 trials/888 infants).

Proportion not fully breastfeeding at three and six months of age
In one study, no significant difference in the rate of infants not fully breastfeeding was observed at three months (RR 1.18, 95% CI [0.88 to 1.58]; 283 infants) or at six months of age (RR 1.31, 95% CI [0.89 to 1.92]; 281 infants). In a further trial reporting on these outcomes, the rate of infants not fully breastfeeding was reduced with supplemental cup feeding at three months (RR 0.43, 95% CI [0.33 to 0.55]; 522 infants), and at six months of age (RR 0.74, 95% CI [0.62 to 0.88]; 522 infants). No meta-analyses were performed due to heterogeneity.

Additional outcomes
Length of hospital stay was statistically significantly longer with cup feeding in one study (MD 10.08 days, 95% CI [3.87 to 16.29]; 301 infants), but not in another trial (MD -0.20 days, 95% CI [-0.58 to 0.18]; 522 infants); no meta-analysis was performed due to heterogeneity. Average time per feed was not statistically significantly different between treatment groups in two trials reporting on this outcome (no meta-analysis was performed due to heterogeneity). In one trial of 78 infants, episodes of oxygen desaturation were not significantly different between cup and bottle groups, and gestational age at discharge did not differ between groups in a further trial of 522 infants (MD -0.10 days, 95% CI [-0.54 to 0.34]).

For all other outcomes, no results were available.

5. Additional author observations*

Using GRADE criteria, evidence for the outcomes weight gain in the first seven days of the study, not breastfeeding at hospital discharge, not fully breastfeeding at hospital discharge, and length of hospital stay was rated as low quality, while evidence for the outcomes not breastfeeding at six months and not fully breastfeeding at six months was rated as very low quality. While three of the five included studies were at low risk of allocation concealment bias, all five studies were at high risk of performance bias due to lack of blinding. In one large study, high levels of non-compliance among the cup-feeding group were reported (56%), with bottles being used. Reasons given for non-compliance included the infant not managing cup feeds, not being satisfied, spilling a lot, or taking too long to feed. In a further large trial, 85 out of 607 enrolled infants were excluded from results due to non-compliance or development of a disease preventing oral feeding. No trials of term infants were identified for inclusion in the review, thus the findings are not generalizable to that population. It is also unclear whether the findings are applicable to low-income settings.

Overall, results demonstrated a benefit of cup feeding over bottle feeding on breastfeeding rates up to six months of age. However, these findings should be interpreted with caution due to heterogeneity in results and the poor quality of evidence. In addition, supplemental feeding by cup may increase length of stay in hospital.

Although there are clear limitations to the included studies, the issues surrounding non-compliance may hinder further research into this area. Moreover, before further trials of cup feeding are undertaken, other interventions aimed at maintaining breastfeeding longer term (e.g., skin to skin contact, rooming in, non-separation of mother and infant, non-introduction of supplemental feeds unless medically indicated, antenatal breastfeeding education) should be explored.