Review question: do preterm or low birth weight infants (babies born early or small) grow faster and have fewer problems when they receive all their nutrients as milk feeds from shortly after birth (compared with gradually introducing milk feeds while giving fluid or nutrients via an intravenous drip (a slow infused into the bloodstream via a vein))?
Background: 'early full enteral feeding' means that preterm or low birth weight infants receive all their nutrition as milk feeds from shortly after birth, and do not receive any supplemental fluids or nutrition via intravenous drips. Assessing whether this approach is safe and beneficial is particularly relevant to feeding very preterm or very low birth weight infants (born before 32 weeks, or birth weigh less than 1500 g).
Study characteristics: we included six trials, all undertaken in neonatal care units in India during the 2010s. The trials were generally good quality although most were small (involving 526 infants in total). Participants were preterm infants of birth weight 1000 g to 1500 g.
The search is up to date as of July 2020.
Key results: there were insufficient data to show whether infants who received full milk feeds from birth put on weight and grew more quickly than those for whom feeds were introduced gradually during the first week or two after birth. The trials reported no information about the effects early full milk feeds might have on development and growth later in the baby's life. The included trials found no evidence of other potential benefits or harms of early full feeds, including any effects on feeding or bowel problems.
Conclusion: there is not enough evidence to determine whether early full milk feeds benefit preterm or low birth weight infants. New trials would be needed to resolve this uncertainty.
Quality of evidence: we assessed this evidence as being of low or very low quality because the included trials were small with some methodological weaknesses and their findings were inconsistent with each other. This means that further research is very likely to have an important impact on the estimates of effect and our confidence in the findings.
Trials provided insufficient data to determine with any certainty how early full enteral feeding, compared with delayed or progressive introduction of enteral feeds, affects growth in preterm or low birth weight infants. We are uncertain whether early full enteral feeding affects the risk of necrotising enterocolitis because of the risk of bias in the trials (due to lack of masking), inconsistency, and imprecision.
The introduction and advancement of enteral feeds for preterm or low birth weight infants is often delayed because of concerns that early full enteral feeding will not be well tolerated or may increase the risk of necrotising enterocolitis. Early full enteral feeding, however, might increase nutrient intake and growth rates; accelerate intestinal physiological, metabolic, and microbiomic postnatal transition; and reduce the risk of complications associated with intravascular devices for fluid administration.
To determine how early full enteral feeding, compared with delayed or progressive introduction of enteral feeds, affects growth and adverse events such as necrotising enterocolitis, in preterm or low birth weight infants.
We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials; MEDLINE Ovid, Embase Ovid, Maternity & Infant Care Database Ovid, the Cumulative Index to Nursing and Allied Health Literature, and clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials to October 2020.
Randomised controlled trials that compared early full enteral feeding with delayed or progressive introduction of enteral feeds in preterm or low birth weight infants.
We used the standard methods of Cochrane Neonatal. Two review authors separately assessed trial eligibility, evaluated trial quality, extracted data, and synthesised effect estimates using risk ratios (RR), risk differences, and mean differences (MD) with 95% confidence intervals (CI). We used the GRADE approach to assess the certainty of evidence.
We included six trials. All were undertaken in the 2010s in neonatal care facilities in India. In total, 526 infants participated. Most were very preterm infants of birth weight between 1000 g and 1500 g. Trials were of good methodological quality, but a potential source of bias was that parents, clinicians, and investigators were not masked. The trials compared early full feeding (60 mL/kg to 80 mL/kg on day one after birth) with minimal enteral feeding (typically 20 mL/kg on day one) supplemented with intravenous fluids. Feed volumes were advanced daily as tolerated by 20 mL/kg to 30 mL/kg body weight to a target steady-state volume of 150 mL/kg to 180 mL/kg/day. All participating infants were fed preferentially with maternal expressed breast milk, with two trials supplementing insufficient volumes with donor breast milk and four supplementing with preterm formula.
Few data were available to assess growth parameters. One trial (64 participants) reported a slower rate of weight gain (median difference –3.0 g/kg/day), and another (180 participants) reported a faster rate of weight gain in the early full enteral feeding group (MD 1.2 g/kg/day). We did not meta-analyse these data (very low-certainty evidence). None of the trials reported rate of head circumference growth. One trial reported that the mean z-score for weight at hospital discharge was higher in the early full enteral feeding group (MD 0.24, 95% CI 0.06 to 0.42; low-certainty evidence). Meta-analyses showed no evidence of an effect on necrotising enterocolitis (RR 0.98, 95% CI 0.38 to 2.54; 6 trials, 522 participants; I² = 51%; very low-certainty evidence).