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.

Gastric Residual Volume in Feeding Advancement in Preterm Infants (GRIP Study): A Randomized Trial.

OBJECTIVE: To evaluate the effect of not relying on prefeeding gastric residual volumes to guide feeding advancement on the time to reach full feeding volumes in preterm infants, compared with routine measurement of gastric residual volumes. We hypothesized that not measuring prefeeding gastric residual volumes can shorten the time to reach full feeds. STUDY DESIGN: In this single-center, randomized, controlled trial, we included gavage fed preterm infants with birth weights (BW) 1500-2000 g who were enrolled within 48 hours of birth. Exclusion criteria were major congenital malformations, asphyxia, and BW below the third percentile. In the study group, the gastric residual volume was measured only in the presence of bloody aspirates, vomiting, or an abnormal abdominal examination. In the control group, gastric residual volume was assessed routinely, and feeding advancement was based on the gastric residual volume. The primary outcome was the time to reach feeding volumes of 120 mL/kg per day. Secondary outcomes were time to regain BW, episodes of feeding interruptions, sepsis, and necrotizing enterocolitis. RESULTS: Eighty-seven infants were enrolled. There were no differences between the study and control groups with respect to time to reach full feeds (6 days [95% CI, 5.5-6.5] vs 5 days [95% CI, 4.5-5.5]; P = .82), time to regain BW, episodes of feeding interruptions, or sepsis. Two infants in the control group developed necrotizing enterocolitis. CONCLUSIONS: Avoiding routine assessment of gastric residual volume before feeding advancement did not shorten the time to reach full feeds in preterm infants with BW between 1500 and 2000 g. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01337622.

Target fortification of breast milk with fat, protein, and carbohydrates for preterm infants.

OBJECTIVES: Fortification of breast milk is an accepted practice for feeding very low birth weight infants, however, fixed dosage enhancement does not address variations in native breast milk. This could lead to deficiencies in calories and macronutrients. We therefore established the infrastructure for target fortification in breast milk by measuring and adjusting fat, protein, and carbohydrate content daily. We analyzed nutrient intake, growth, and safety variables. STUDY DESIGN: Each 12-hour batch of breast milk was analyzed using near-infrared spectroscopy. Macronutrients were individually added to routine fortification to achieve final contents for fat (4.4 g), protein (3 g), and carbohydrates (8.8 g) (per 100 mL). Fully breast milk fed healthy very low birth weight infants (<32 weeks) were fed the fortified breast milk for at least 3 weeks. Matched pair analysis of 20 infants fed routinely fortified breast milk was performed using birth weight, gestational age, and postnatal age. RESULTS: All 650 pooled breast milk samples required at least 1 macronutrient adjusted. On average, 0.3 ± 0.4 g of fat, 0.7 ± 0.2 g of protein, and 1.2 ± 0.2 g of carbohydrate were added. Biochemistry was normal in the 10 target fortified infants (birth weight: 860 ± 309 g, 26.3 ± 1.6 weeks gestational age); weight gain was 19.9 ± 2.7 g/kg/d; and milk intake was 147 ± 5 mL/kg/d (131 ± 16 kcal/kg/d). Osmolality of fortified breast milk was 436 ± 13 mOsmol/kg. Matched pair analysis of infants indicated a higher milk intake (155 ± 5 mL/kg/d) but similar weight gain (19.7 ± 3.3 g/kg/d). No adverse event was observed. The linear relationship between milk intake and weight gain observed in study babies but not seen in matched controls may be related to the variable composition of breast milk. CONCLUSIONS: Daily target fortification can be safely implemented in clinical routine and may improve growth.

Continuous nasogastric milk feeding versus intermittent bolus milk feeding for premature 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 theoretical benefits and risks of each method have been proposed, effects on clinically important outcomes remain uncertain. OBJECTIVES: To examine the evidence regarding the effectiveness of continuous versus intermittent bolus nasogastric milk feeding in premature infants less than 1500 grams. SEARCH METHODS: Searches were performed of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2011), MEDLINE, CINAHL and HealthSTAR up to July 2011. SELECTION CRITERIA: Randomised and quasi-randomised clinical trials comparing continuous versus intermittent bolus nasogastric milk feeding in premature infants less than 1500 grams. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all trials for relevance and methodologic quality. The standard methods of the Cochrane Neonatal Review Group were used to extract data. MAIN RESULTS: Overall, the seven included trials, involving 511 infants, found no differences in time to achieve full enteral feeds between feeding methods (weighted mean difference (WMD) 2 days; 95% CI -0.3 to 3.9) . In the subgroup analysis of those studies comparing continuous nasogastric versus intermittent bolus nasogastric milk feedings the findings remained unchanged (WMD 2 days, 95% CI -0.4 to 4.1). There was no significant difference in somatic growth and incidence of NEC between feeding methods irrespective of tube placement. One study noted a trend toward more apneas during the study period in infants fed by the continuous tube feeding method compared to those fed by intermittent feedings delivered predominantly by orogastric tube placements [mean difference (MD) 14.0 apneas during study period; 95% CI -0.2 to 28.2]. In subgroup analysis based on weight groups, one study suggested that infants less than 1000 grams and 1000 to 1250 grams birth weight gained weight faster when fed by the continuous nasogastric tube feeding method compared to intermittent nasogastric tube feeding method (MD 2.0 g/day; 95% CI 0.5 to 3.5; MD 2.0 g/day; 95% CI 0.2 to 3.8, respectively). A trend toward earlier discharge for infants less than 1000 grams birth weight fed by the continuous tube feeding method compared to intermittent nasogastric tube feeding method (MD -11 days; 95% CI -21.8 to -0.2). AUTHORS' CONCLUSIONS: Small sample sizes, methodologic limitations, inconsistencies in controlling variables that may affect outcomes, and conflicting results of the studies to date make it difficult to make universal recommendations regarding the best tube feeding method for premature infants less than 1500 grams. The clinical benefits and risks of continuous versus intermittent nasogastric tube milk feeding cannot be reliably discerned from the limited information available from randomised trials to date.

Individualized target fortification of breast milk with protein, carbohydrates, and fat for preterm infants: A double-blind randomized controlled trial.

BACKGROUND & AIMS: In preterm infants, natural variation of breast milk composition makes it difficult to achieve recommended macronutrient intakes with standard fortification. Evidence suggests that nutritional deficiency induces poor postnatal growth. This study investigates impacts of target fortification on preterm growth and metabolism by adjusting breast milk macronutrients. METHODS: This study was conducted as a single-centre, double-blind, randomized controlled trial for infants <30 gestational weeks. The control group received standard fortification and the intervention group received standard plus target fortification adding modular protein, lipids, and carbohydrates. Breast milk content was measured 3x/week using a validated near-infrared bedside spectrometer (NIRS). Modulars were added to achieve recommended values. To assess total nutrient intake, all 2810 native breast milk samples were analyzed - protein and fat using bedside-NIRS, lactose using tandem mass spectrometry (UPLC-MS/MS). Body composition was measured using air displacement plethysmography. Primary outcome was weight gain during the first 21 days of intervention. RESULTS: Baseline characteristics, morbidities, and total fluid intake were not different between groups (intervention n = 52, control n = 51). The intervention group infants had higher macronutrient intakes, weight gain (21.2 ± 2.5 vs 19.3 ± 2.4 g/kg/d, mean difference: 1.9 g/kg/d, 95% CI: 0.9 - 2.9), and body weight. Infants in the intervention group from mothers with below-average breast milk protein content showed greatest impact on weight at 36 weeks (2580 ± 280 g vs 2210 ± 300 g), length, head circumference, fat, and fat-free mass. Also, feeding intolerance was less frequent, blood urea was higher, and triglycerides were lower. CONCLUSIONS: This study provides evidence that target fortification of breast milk with low macronutrient content enhances the quality of nutrition and growth and is feasible in clinical routine.

Guidelines for feeding very low birth weight infants.

Despite the fact that feeding a very low birth weight (VLBW) neonate is a fundamental and inevitable part of its management, this is a field which is beset with controversies. Optimal nutrition improves growth and neurological outcomes, and reduces the incidence of sepsis and possibly even retinopathy of prematurity. There is a great deal of heterogeneity of practice among neonatologists and pediatricians regarding feeding VLBW infants. A working group on feeding guidelines for VLBW infants was constituted in McMaster University, Canada. The group listed a number of important questions that had to be answered with respect to feeding VLBW infants, systematically reviewed the literature, critically appraised the level of evidence, and generated a comprehensive set of guidelines. These guidelines form the basis of this state-of-art review. The review touches upon trophic feeding, nutritional feeding, fortification, feeding in special circumstances, assessment of feed tolerance, and management of gastric residuals, gastro-esophageal reflux, and glycerin enemas.

A case study utilizing an enteral refeeding technique in a premature infant with short bowel syndrome.

Premature and full-term infants may be born with congenital abnormalities or develop acquired lesions of the gastrointestinal tract that require the placement of an enterostomy. Enterostomies can result in significant segments of excluded small bowel, creating a functional short bowel syndrome. Infants with enterostomies can develop dehydration, electrolyte imbalance, and failure to thrive. An illustrative case report of a premature infant with short bowel syndrome treated with enteral refeedings via a mucous fistula is presented. This report highlights the lessons learned from the interdisciplinary team's collective 10-year experience with enteral refeeding in infants with enterostomies. The physiologic basis for this approach is reviewed and literature reports are outlined. The specific nursing care and step-by-step techniques to deliver enteral refeeding through the mucous fistula are provided along with implications for clinical practice, education, and research.

Evidence-based feeding guidelines for very low-birth-weight infants.

Clinical practice guidelines (CPG) for the nutritional management of premature infants are limited. This project focused on the development of a research-based enteral feeding CPG for infants of < 1,500 g. The CPG was based on an extensive literature review and developed through a process of consensus decision making by a team of clinical researchers. Infants that weigh < 1,000 g initiate minimal enteral nutrition (MEN) at 48 hours; nutritional feedings begin on day 5 to 6 of life. For infants between 1,000 and 1,500 g, nutritional feedings begin at 48 hours and are advanced at a rate of less than 30 mL/kg per day. The benefits and risks of continuous versus intermittent nasogastric tube feeding were inconclusive; therefore, the CPG does not stipulate a feeding method. Breast milk is used preferentially, and specific guidelines for the definition and management of feeding intolerance are provided. A follow-up study testing this CPG has been completed and is published in the original research section of this issue.

A matched cohort study of feeding practice guidelines for infants weighing less than 1,500 g.

PURPOSE: To evaluate the efficacy and safety of clinical practice guidelines (CPG) for the nutritional management of infants weighing < 1,500 g. SUBJECTS: Infants weighing < 1,500 g (n = 200) admitted to the NICU who had no major congenital anomalies were enrolled. DESIGN AND METHODS: A before-and-after matched cohort study was conducted during 1996/1997 and 1998/1999 enrolling infants in a Standard Practice (SP) group and CPG group, respectively. Weight-stratified CPG were introduced between these 2 study periods. Data on the first 100 babies who could be matched for birth weight and gestational age were analyzed. Data collection continued until full feedings were established and tolerated for 48 hours or the infant was discharged from the hospital, whichever came first. PRIMARY OUTCOME MEASURE: Of the 200 infants in the study (median gestational age 28 weeks), 142 infants attained full feedings. The median time to full feedings was 15 days in both groups, and a paired sample t test showed no significant difference between the 2 groups (P = 0.35). PRINCIPAL RESULTS: No statistically significant differences in the age of feeding commencement, number of feeding interruptions, days on total parenteral nutrition, days to regain birth weight, age at discharge, incidence of sepsis, necrotizing enterocolitis, or use of erythromycin were found. CONCLUSIONS: The CPG was a safe alternative to standardize nutritional practices in the NICU. The lack of differences between groups shown in this study is likely related to gut immaturity limiting the infant's response to changes in feeding practices, inconsistent use of the guidelines, confounding factors, the small sample size, or the similarity between SP and the CPG.