Review question
Does giving preterm (born at < 37 weeks) or low birth weight (< 2500 grams) infants a greater volume of feeds than is usually given, promote growth without causing feeding problems or other side effects?
Background
Infants born early (preterm) need extra nutrients for growth. One way to deliver extra nutrition is to give infants a greater volume of feeds than usual (high volume feeds, equal to or greater than 180 to 200 mL/kg/day of milk). Although giving high volumes of milk to preterm or low birth weight infants might increase growth rates, there are concerns that infants may not tolerate high volume feeds and may experience side effects including severe bowel problems. We have looked for evidence from clinical trials that assessed whether high volume feeds are beneficial or harmful for preterm or low birth weight infants.
Study characteristics
Search is up-to-date as of June 2020. We found three studies that addressed this question.
Key results
Evidence from two studies showed that high volume feeds (≥ 180 mL/kg/day) with fortified human milk (human milk with added human milk fortifier) or preterm formula probably improves weight gain during hospital stay, when compared to standard volume of the same. Similarly, evidence from one small study showed that high volume feeds (≥ 200 mL/kg/day) with unfortified human milk or preterm formula probably improves weight gain during hospital stay. The evidence is insufficient to comment on the effect of high volume feeds on increase in length or head size during hospital stay, long-term growth and development, and the effect on gut problems or other side effects.
Conclusions
High volume feeds probably improve weight gain during hospital stay. The available data is inadequate to draw conclusions on the effect of high volume feeds on other growth and clinical outcomes.
High volume feeds (≥ 180 mL/kg/day of fortified human milk or preterm formula, or ≥ 200 mL/kg/day of unfortified human milk or term formula) probably improves weight gain during hospital stay. The available data is inadequate to draw conclusions on the effect of high volume feeds on other growth and clinical outcomes. A large RCT is needed to provide data of sufficient quality and precision to inform policy and practice.
Human milk is the best enteral nutrition for preterm infants. However, human milk, given at standard recommended volumes, is not adequate to meet the protein, energy, and other nutrient requirements of preterm or low birth weight infants. One strategy that may be used to address the potential nutrient deficits is to give a higher volume of enteral feeds. High volume feeds may improve nutrient accretion and growth, and in turn may improve neurodevelopmental outcomes. However, there are concerns that high volume feeds may cause feed intolerance, necrotising enterocolitis, or complications related to fluid overload such as patent ductus arteriosus and chronic lung disease.
This is an update of a review published in 2017.
To assess the effect on growth and safety of high versus standard volume enteral feeds in preterm or low birth weight infants. In infants who were fed fortified human milk or preterm formula, high and standard volume feeds were defined as > 180 mL/kg/day and ≤ 180 mL/kg/day, respectively. In infants who were fed unfortified human milk or term formula, high and standard volume feeds were defined as > 200 mL/kg/day and ≤ 200 mL/kg/day, respectively.
We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020 Issue 6) in the Cochrane Library; Ovid MEDLINE (1946 to June 2020); Embase (1974 to June 2020); and CINAHL (inception to June 2020); Maternity & Infant Care Database (MIDIRS) (1971 to April 2020); as well as previous reviews, and trial registries.
We included randomised controlled trials (RCTs) that compared high versus standard volume enteral feeds for preterm or low birth weight infants.
Two review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) and risk difference for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence. The primary outcomes were weight gain, linear and head growth during hospital stay, and extrauterine growth restriction at discharge.
We included two new RCTs (283 infants) in this update. In total, we included three trials (347 infants) in this updated review.
High versus standard volume feeds with fortified human milk or preterm formula
Two trials (283 infants) met the inclusion criteria for this comparison. Both were of good methodological quality, except for lack of masking. Both trials were performed in infants born at < 32 weeks' gestation. Meta-analysis of data from both trials showed high volume feeds probably improves weight gain during hospital stay (MD 2.58 g/kg/day, 95% CI 1.41 to 3.76; participants = 271; moderate-certainty evidence). High volume feeds may have little or no effect on linear growth (MD 0.05 cm/week, 95% CI -0.02 to 0.13; participants = 271; low-certainty evidence), head growth (MD 0.02 cm/week, 95% CI -0.04 to 0.09; participants = 271; low-certainty evidence), and extrauterine growth restriction at discharge (RR 0.71, 95% CI 0.50 to 1.02; participants = 271; low-certainty evidence). We are uncertain of the effect of high volume feeds with fortified human milk or preterm formula on the risk of necrotising enterocolitis (RR 0.74, 95% CI 0.12 to 4.51; participants = 283; very-low certainty evidence).
High versus standard volume feeds with unfortified human milk or term formula
One trial with 64 very low birth weight infants met the inclusion criteria for this comparison. This trial was unmasked but otherwise of good methodological quality. High volume feeds probably improves weight gain during hospital stay (MD 6.2 g/kg/day, 95% CI 2.71 to 9.69; participants = 61; moderate-certainty evidence). The trial did not provide data on linear and head growth, and extrauterine growth restriction at discharge. We are uncertain as to the effect of high volume feeds with unfortified human milk or term formula on the risk of necrotising enterocolitis (RR 1.03, 95% CI 0.07 to 15.78; participants = 61; very low-certainty evidence).