No Benefits of Slow Feed Advancement Rate as Compared to Fast Feed Advancement Rate on Mortality and Morbidity for Preterm and Low Birthweight Infants: Results of a Systematic Review and Meta-analysis

Background: Preterm and low birthweight infants are at increased risk for necrotizing enterocolitis and feed intolerance. Slow advancement of enteral feeding may prevent necrotizing enterocolitis, but may also increase the risk of infections and liver disease secondary to extended parenteral nutrition. Given the potential benefits and risks of slow feed advancement, the optimal rate of feed advancement remains unclear in clinical practice.

Methods: We searched databases including Medline, Scopus, Web of Science, CINAHL, and Index Medicus to identify randomized controlled trials that compared the effects of slow versus fast feed advancement rates on mortality, morbidity, growth, and neurodevelopmental outcomes. We systematically extracted data from eligible studies and pooled the relative risks or mean differences comparing slow versus fast feeding advancement using random effects meta-analysis. We assessed the quality of each study using Cochrane’s Risk of Bias 2 tool and summarized the overall quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method.

Results: We identified 3,174 studies in the search and found 12 that were eligible for inclusion. Slow feed advancement did not affect the risk of mortality (9 studies; 3602 participants; pooled RR 1.12; 95% CI 0.88, 1.42; I2=12.2%, p-value=0.33), risk of necrotizing enterocolitis (12 studies; 3975 participants; pooled RR 1.10; 95% CI 0.85, 1.43; I2=0.0%, p-value=0.45), risk of feed intolerance (8 studies; 909 participants; pooled RR 1.10; 95% CI 0.91, 1.33; I2=0.0%, p-value=0.85), risk of sepsis (9 studies; 3603 participants; pooled RR 1.09; 95% CI 0.98, 1.21; I2=0.0%, p-value=0.54), or risk of apnea (3 studies; 248 participants; pooled RR 1.34; 95% CI 0.94, 1.91; I2=0.0%, p-value=0.90). Infants in slow feed advancement groups took an additional 3.07 days (95% CI 2.31, 3.82; I2=0.0%; p-value=0.61; 5 studies; 693 participants) to regain birth body weight and spent additional 2.26 days (95% CI 0.46, 4.06; I2=50.9%; p-value=0.06; 6 studies; 3564 participants) in the hospital as compared to those in fast feed advancement groups. Our subgroup analysis found similar results among infants with birthweight less than 1000g. In addition, the effect of slow feed advancement on mortality, necrotizing enterocolitis, sepsis, and feed intolerance did not differ by the absolute volume of feed advancement; the effect of slow feed advancement on necrotizing enterocolitis did not differ by milk type.

Conclusion: Preterm and low birthweight infants fed at a slow advancement rate regained their birth body weight slower and had longer hospital stay without reducing risks of mortality and morbidity, as compared to infants fed at a fast advancement rate. Fast advancement rates should be adopted with cautions among clinically stable preterm and low birthweight infants.