Dilute versus full strength formula in exclusively formula-fed preterm or low birth weight infants

Preterm infants have fewer nutrient reserves at birth than full term infants and often receive artificial formula feeds in the absence of expressed breast milk. Although it is generally agreed that feeding must be initiated slowly and advanced with much greater deliberation than in a healthy, full term infant, the way in which feeds are introduced and advanced in preterm infants varies widely. This review focuses on whether dilute or full strength formula is the preferable mode of introducing feeds in preterm infants.

To assess the effects of dilute versus full strength formula on the incidence of necrotising enterocolitis, feeding intolerance, weight gain, length of stay and time to achieve full calorie intake in exclusively formula-fed preterm or low birth weight infants. A secondary objective was to assess the effects of different dilution strategies.

We used the standard search methods of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 1), MEDLINE (1946 to February 2013) and EMBASE (1974 to February 2013).

Randomised or quasi-randomised trials comparing strengths of formula milk in exclusively formula-fed preterm or low birth weight infants. Studies were excluded if infants received formula as a supplement to breast milk.

We independently assessed studies for inclusion. We collected data using the standard methods of the Cochrane Neonatal Review Group, with independent assessment of risk of bias and data extraction. We synthesised mean differences using a fixed-effect meta-analysis model.

Three studies involving 102 preterm or low birth weight infants were included in the review. The studies compared dilute (double volume, half strength) formula with full strength (20 kcal/oz) formula. We assessed all three studies as being at unclear risk of bias due to the likely absence of blinding of study personnel and the potential for selection bias in the largest trial. Data for the primary outcome of necrotising enterocolitis were not reported in any of the studies. Two of the studies (88 infants) could be combined in the meta-analysis. Infants in the dilute formula with double volume (half strength) group had significantly fewer episodes of feeding intolerance. Infants in the dilute formula with double volume (half strength) group had fewer episodes of gastric residuals per day (one study, mean difference (MD) -1.20, 95% confidence interval (CI) -2.2 to -0.2), fewer episodes of gastric residuals per baby until attaining 100 kcal/kg (one study, MD -0.80, 95% CI -1.32 to -0.28), fewer episodes of vomiting per day (one study, MD -0.04, 95% CI -0.07 to -0.01) and fewer occurrences of abdominal distension greater than 2 cm (two studies, MD -0.16, 95% CI -0.19 to -0.13). For the secondary outcomes, infants in the dilute formula with double volume (half strength) group attained an adequate energy intake significantly earlier than infants in the full strength group (two studies, MD -2.26, 95% CI -2.85 to -1.67). For weight gain one week after commencement of intragastric feeds, the difference between groups was not statistically significant (one study, MD 0.05 kg, 95% CI -0.06 to 0.15). Data were not reported for length of hospital stay.

There is evidence from three small, old trials at unclear risk of bias that use of dilute formula in preterm or low birth weight formula-fed infants leads to an important reduction in the time taken for these infants to attain an adequate energy intake. There was no evidence of important differences in feeding intolerance. The impact on serious gastrointestinal problems, including necrotising enterocolitis, was not reported. Further randomised trials are needed to confirm these results.