MANUSCRIPT CITATION

Parker LA, Weaver M, Torrazza RJM, Shuster J, Li N, Krueger C, Neu J. Effect of Gastric Residual Evaluation on Enteral Intake in Extremely Preterm Infants: A Randomized Clinical Trial. JAMA Pediatr 2019;173(6):534-543. PMID 31034045.

REVIEWED BY

Dr Lucy Hare, BMBS, BMedSci.
University Hospitals of Leicester NHS Trust and University of Leicester

Professor Elaine Boyle, MBChB, MSc, MD, PhD.
University Hospitals of Leicester NHS Trust and University of Leicester

TYPE OF INVESTIGATION

Interventions

QUESTION

(P) For infants born at ≤32 weeks of gestation with birthweights ≤1250g who receive some feeds by 72 hours of age, (I) is omitting prefeed gastric residual evaluations, (C) compared to undertaking prefeed gastric residual evaluations, (O) associated with improved nutritional outcomes (T) over the first 6 weeks after birth?

METHODS

• Design: Single-centre randomised controlled trial.
• Allocation: Infants were randomly allocated into the ‘Residual’ and ‘No Residual’ groups using a computer-based permuted block randomisation system. Allocation was concealed.
• Blinding: Blinding was not possible after the randomisation process because the act of taking and recording gastric residuals was physically evident to all involved.
• Follow-up period: Infants were followed up for 6 weeks after birth.
• Setting: A single level 4 neonatal intensive care unit (NICU) in America between 17th October 2013 and 8th October 2016.
• Patients:
  • Inclusion criteria – infants were eligible for inclusion if they met all of the following:
    • Gestational age ≤32 weeks;
    • Birth weight ≤1250g;
    • Received some feeds within 72 hours of birth;
    • Enrolled within 72 hours of birth and within 24 hours of feeding initiation.
  • Exclusion criteria – infants were excluded if they had any of the following:
    • Congenital or chromosomal abnormalities;
    • Lack of parental written informed consent;
    • Not expected to survive;
    • Enrolled in another study prohibiting participation.
  • Withdrawal criteria – infants that were included, were subsequently withdrawn if they developed any of the following:
    • Necrotising enterocolitis (NEC) ≥ Stage II;
    • Spontaneous intestinal perforation;
    • Death.
• Intervention: Infants were allocated to either: the ‘No Residual’ group, in which no prefeed gastric residual measurements were taken; or the ‘Residual’ group, in which routine prefeed gastric residual measurements were taken.
• Outcomes:
  • Primary outcome: The weekly amount of enteral nutrition provided to infants in the first 6 weeks of life.
  • Secondary outcomes:
    • Secondary nutritional outcomes:
      1. Days to full feeds (120mL/kg/day)
      2. Hours of parenteral nutrition (PN)
      3. Hours with a central line
      4. PN-associated liver disease – assessed via:
         • Bilirubin levels;
         • Alkaline phosphatase (ALP) levels.
      5. Feeding intolerance – assessed via:
         • Episodes of emesis;
         • Episodes of abdominal circumference increasing by >2cm;
         • Number of abdominal radiographs.
      6. Growth – assessed via weekly:
         • Weight;
         • Head circumference;
         • Length.
    • Other secondary outcomes:
      1. Days to discharge;
      2. Presumed or culture-proven late-onset sepsis;
      3. NEC ≥ Stage II;
      4. Intraventricular haemorrhage (IVH);
      5. Bronchopulmonary dysplasia (BPD);
      6. Duration of respiratory support;
      7. Gastric content aspiration/ventilator-associated pneumonia (VAP) – assessed via:
         • Evidence of VAP on a chest radiograph;
         • Positive tracheal aspirate samples.
      8. Death.
    • Secondary outcomes collected but not included in this paper:
      1. Occult faecal blood;
      2. Faecal calprotectin;
      3. S100A12 levels;
      4. Motilin levels;
      5. Gastrin levels.
• Analysis and Sample Size:
  • Power calculations – 104 infants were needed to achieve 80% power for the primary outcome. More than 104 infants were recruited to allow for attrition.
  • Patients Included – 146 infants were randomised; 74 to the ‘Residual’ group, and 72 to the ‘No Residual’ group. The two groups had similar baseline characteristics, except for ethnicity. After randomisation 3 infants in the ‘No Residual’ group had to be excluded because the parents withdrew consent, or the infant did not meet the inclusion criteria. Of the remaining 143 infants, 118 were followed up until discharge, and 25 were followed up until withdrawal. 7 infants were withdrawn due to death, 11 due to NEC, and 4 due to intestinal perforation. Reason for withdrawal is not clearly documented for 3 of the infants, but it seems most likely that they were lost to follow up.
  • Statistical analysis – A variety of different statistical analyses were used. These included generalised linear mixed model analyses, survival analyses and Wilcoxon 2-sample tests. A p value of <0.05 was considered statistically significant. All infants (74 in the ‘Residual’ group, and 69 in the ‘No Residual’ group) were included in the modified intent-to-treat analysis.

MAIN RESULTS

Primary outcome:

The results show that infants in the ‘No Residual’ group had a greater enteral nutrition intake in weeks 5 and 6 of life, and a greater mean weekly increase in enteral nutrition intake overall. However, there was no difference in enteral nutrition intake in weeks 1-4 of life between the two groups. This can be seen in the table below, which is adapted from the referenced study.

Outcomes were analysed using generalised linear mixed model analysis. Estimates are displayed as least square means unless otherwise specified. Significant differences between the groups are in bold.

Secondary outcomes:

Secondary nutritional outcomes:

The results show that infants in the ‘No Residual’ group had more episodes of emesis, but fewer episodes of abdominal distention, and a greater increase in weight. However, there was no difference in any of the other secondary nutritional outcomes between the two groups. This can be seen in the table below, which is adapted from the referenced study.

Outcomes 1-3 were analysed using survival analysis, and outcomes 4-6 (excluding 4C) using generalised linear mixed model analysis. Transformed values are presented. Estimates are displayed as least square means unless otherwise specified. Significant differences between the groups are in bold.

Other secondary outcomes:

The results show that infants in the ‘No Residual’ group were discharged more quickly from hospital, when gestational age was accounted for. The untransformed days to discharge values were 86.4 days (95% CI 80.7 – 92.1 days) in the ‘Residual’ group and 79.1 days (95% CI 73.17 – 84.5 days) in the ‘No Residual’ group. However, there was no difference in any of the other secondary outcomes between the two groups. The results can be seen in the table below, which is adapted from the referenced study.

Outcomes 1 and 6B were analysed using survival analysis, and the rest of the outcomes using generalised linear mixed model analysis. Transformed values are presented. Estimates are displayed as least square means unless otherwise specified. Significant differences between the groups are in bold. Positive tracheal aspirate is the only result displayed relating to gastric aspiration/VAP because no infants in the study had evidence of VAP on a chest radiograph.

CONCLUSION

Omitting prefeed gastric residual evaluation led to improved nutritional outcomes over the first 6 weeks after birth. It increased the amount of enteral nutrition received and resulted in greater weight gain, even though it did lead to more episodes of emesis. However omission did not affect the amount of time taken to reach full feeds, the amount of time PN or respiratory support was required, or complication rates. Therefore, the authors suggest that we should only undertake gastric residual evaluations when infants have symptoms of gastro-intestinal disturbance, rather than undertaking them routinely.

COMMENTARY

Prefeed gastric residuals are routinely evaluated in many NICUs. Evaluation aims to detect feed intolerance that might be associated with early NEC, and to reduce aspiration and VAP. However, evidence behind this practice is limited.(1-3) It may reduce nutritional intake when feeds are stopped based on subjective assessments.(1-5) This is concerning because adequate nutrition is essential for growth and neurodevelopment.(1,3,6)

This study investigates routine prefeed gastric residual evaluation, and is the first study to evaluate its effects on VAP rates. The authors suggest that omitting evaluation leads to increased nutritional intake, improved weight gain and earlier hospital discharge. They also suggest that omission appears safe because it does not impact VAP or NEC rates.

The study design has strengths and limitations. One strength is that the primary outcome is adequately powered. However, secondary outcomes are not, and NEC is arguably the most important outcome.(3) Furthermore, evaluating the primary outcome over six weeks may not be a valid measure; the greatest nutritional deficits usually occur in the first two weeks after birth.

Other strengths are the attempts to reduce bias. Performance bias was reduced through blinding during group allocation, and attrition bias by including all infants in modified intent-to-treat analysis. However, performance bias may remain as blinding was impossible after group allocation. Reporting bias may also exist as some secondary outcomes were not reported.

A limitation is the single-centre study design as the results may not be generalisable to centres with different feeding protocols. For example, many units quantify full feeds as 150mL/kg/day rather than 120mL/kg/day, and feed intolerance may be more likely with larger volumes. Another limitation is that multiple statistical analyses may make interpreting the results’ clinical implications  difficult for some readers.

Additionally, confounders may exist. Attempts to reduce confounding included: randomisation; excluding infants with congenital conditions; only using human milk; using the NICU’s guidelines for all decisions except the study intervention; and omitting gastric aspiration to check nasogastric tube placement. However, the ‘No Residual’ group had a higher number of African-American infants, who tend to have poorer health outcomes.(7) Also, 26.1% of the ‘No Residual’ group had gastric aspirations performed inadvertently or due to gastro-intestinal symptoms. Furthermore, medications may have impacted feed tolerance.(3,8) Lastly, only using human milk means that the results may not be generalisable to formula-fed infants, and some might argue that omitting gastric aspiration in nasogastric tube placement is unsafe.

Overall, despite limitations, the study design is appropriate. Results are consistent with other literature suggesting that omitting prefeed gastric residual evaluation improves nutritional outcomes(2-5,9) without increasing complications.(2,4-5,9) Given the importance of infant nutrition, it would seem reasonable to omit prefeed gastric residuals in clinical practice for the population studied here. Gastric residuals would only be evaluated if infants had gastro-intestinal symptoms. However, changes in practice would need monitoring, with particular focus on complication rates and long-term outcomes. Further research would also be required to investigate the suitability of this practice for NICUs with different feeding protocols, formula-fed infants, and infants of other gestations and weights.

REFERENCES

1. Li YF, Lin HC, Torrazza RM, Parker L, Talaga E, Neu J. Gastric residual evaluation in preterm neonates: a useful monitoring technique or a hindrance? Pediatr Neonatol 2014; 55(5): 335-340.
2. Torrazza RM, Parker LA, Li Y, Talaga E, Shuster J, Neu J. The value of routine evaluation of gastric residuals in very low birth weight infants. J Perinatol 2015; 35(1): 57-60.
3. Abiramalatha T, Thanigainathan S, Ninan B. Routine monitoring of gastric residual for prevention of necrotising enterocolitis in preterm infants. Cochrane Database Syst Rev 2019; 7: CD012937.
4. Riskin A, Cohen K, Kugelman A, Toropine A, Said W, Bader D. The Impact of Routine Evaluation of Gastric Residual Volumes on the Time to Achieve Full Enteral Feeding in Preterm Infants. J Pediatr 2017; 189: 128-134.
5. Kaur A, Kler N, Saluja S, Modi M, Soni A, Thakur A, et al. Abdominal circumference or gastric residual volume as measure of feed intolerance in VLBW infants. J Pediatr Gastroenterol Nutr 2015; 60(2): 259-263.
6. Ehrenkranz RA, Dusick AM, Vohr BR, Wright LL, Wrage LA, Poole WK. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics 2006; 117(4): 1253-1261.
7. Dominguez TP. Adverse birth outcomes in African American women: the social context of persistent reproductive disadvantage. Soc Work Public Health 2011; 26(1): 3-16.
8. Nakajima J, Sunohara D, Kawashima H. Efficacy of macrolides on gastric motility in extremely low birth weight infants. J Neonatal Perinatal Med 2019; 12(3): 295-300.
9. Barr PA, Mally PV, Caprio MC. Standardized Nutrition Protocol for Very Low-Birth-Weight Infants Resulted in Less Use of Parenteral Nutrition and Associated Complications, Better Growth, and Lower Rates of Necrotizing Enterocolitis. JPEN J Parenter Enteral Nutr 2019; 43(4): 540-549.