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Continuous nasogastric milk feeding versus intermittent bolus milk feeding for preterm infants less than 1500 grams.

BACKGROUND
Milk feedings can be given via nasogastric tube either intermittently, typically over 10 to 20 minutes every two or three hours, or continuously, using an infusion pump. Although the theoretical benefits and risks of each method have been proposed, their effects on clinically important outcomes remain uncertain.  OBJECTIVES: To examine the evidence regarding the effectiveness of continuous versus intermittent bolus tube feeding of milk in preterm infants less than 1500 grams.


SEARCH METHODS
We used the standard search strategy of Cochrane Neonatal to run comprehensive searches in the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 7) in the Cochrane Library; Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions; and CINAHL (Cumulative Index to Nursing and Allied Health Literature) on 17 July 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs.


SELECTION CRITERIA
We included RCTs and quasi-RCTs comparing continuous versus intermittent bolus nasogastric milk feeding in preterm infants less than 1500 grams.


DATA COLLECTION AND ANALYSIS
Two review authors independently assessed all trials for relevance and risk of bias. We used the standard methods of Cochrane Neonatal to extract data. We used the GRADE approach to assess the certainty of evidence. Primary outcomes were: age at full enteral feedings; feeding intolerance; days to regain birth weight; rate of gain in weight, length and head circumference; and risk of necrotising enterocolitis (NEC).


MAIN RESULTS
We included nine randomised trials (919 infants) in this updated Cochrane Review. One study is awaiting classification. Seven of the nine included trials reported data from infants with a maximum weight of between 1000 grams and 1400 grams. Two of the nine trials included infants weighing up to 1500 grams. Type(s) of milk feeds varied, including human milk (either mother's own milk or pasteurised donor human milk), preterm formula, or mixed feeding regimens. In some instances, preterm formula was initially diluted. Earlier studies also used water to initiate feedings. We judged six trials as unclear or high risk of bias for random sequence generation. We judged four trials as unclear for allocation concealment. We judged all trials as high risk of bias for blinding of care givers, and seven as unclear or high risk of bias for blinding of outcome assessors. We downgraded the certainty of evidence for imprecision, due to low numbers of participants in the trials, and/or wide 95% confidence intervals, and/or for risk of bias. Continuous compared to intermittent bolus (nasogastric and orogastric tube) milk feeding Babies receiving continuous feeding may reach full enteral feeding almost one day later than babies receiving intermittent feeding (mean difference (MD) 0.84 days, 95% confidence interval (CI) -0.13 to 1.81; 7 studies, 628 infants; low-certainty evidence).  It is uncertain if there is any difference between continuous feeding and intermittent feeding in terms of number of days of feeding interruptions (MD -3.00 days, 95% CI -9.50 to 3.50; 1 study, 171 infants; very low-certainty evidence). It is uncertain if continuous feeding has any effect on days to regain birth weight (MD -0.38 days, 95% CI -1.16 to 0.41; 6 studies, 610 infants; low-certainty evidence). The certainty of evidence is low and the 95% confidence interval is consistent with possible benefit and possible harm. It is uncertain if continuous feeding has any effect on rate of gain in weight compared with intermittent feeding (standardised mean difference (SMD) 0.09, 95% CI -0.27 to 0.46; 5 studies, 433 infants; very low-certainty evidence). Continuous feeding may result in little to no difference in rate of gain in length compared with intermittent feeding (MD 0.02 cm/week, 95% CI -0.04 to 0.08; 5 studies, 433 infants; low-certainty evidence). Continuous feeding may result in little to no difference in rate of gain in head circumference compared with intermittent feeding (MD 0.01 cm/week, 95% CI -0.03 to 0.05; 5 studies, 433 infants; low-certainty evidence). It is uncertain if continuous feeding has any effect on the risk of NEC compared with intermittent feeding (RR 1.19, 95% CI 0.67 to 2.11; 4 studies, 372 infants; low-certainty evidence). The certainty of evidence is low and the 95% confidence interval is consistent with possible benefit and possible harm.


AUTHORS' CONCLUSIONS
Although babies receiving continuous feeding may reach full enteral feeding slightly later than babies receiving intermittent feeding, the evidence is of low certainty. However, the clinical risks and benefits of continuous and intermittent nasogastric tube milk feeding cannot be reliably discerned from current available randomised trials. Further research is needed to determine if either feeding method is more appropriate for the initiation of feeds. A rigorous methodology should be adopted, defining feeding protocols and feeding intolerance consistently for all infants. Infants should be stratified according to birth weight and gestation, and possibly according to illness.