|
 
 |
| EBN SYNOPSIS |
|
| Year : 2012 | Volume
: 1
| Issue : 4 | Page : 181-183 |
|
Early or delayed enteral feeding for preterm growth-restricted infants: A randomized trial
Fahad Al Hazzani
Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, P. O. Box - 3354, MBC 58, Riyadh, Saudi Arabia
| Date of Web Publication | 12-Jan-2013 |
Correspondence Address:
Fahad Al Hazzani
Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, P. O. Box - 3354, MBC 58, Riyadh
Saudi Arabia
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2249-4847.105975
How to cite this article:
Al Hazzani F. Early or delayed enteral feeding for preterm growth-restricted infants: A randomized trial. J Clin Neonatol 2012;1:181-3 |
| Context | |  |
Growth-restricted preterm infants are at increased risk of developing necrotizing enterocolitis (NEC), and initiation of enteral feeding is frequently delayed. There is no evidence that this delay is beneficial, and it might further compromise nutrition and growth. [1]
The Abnormal Doppler Enteral Prescription Trial (ADEPT) was designed to evaluate the effect of an early compared with a late enteral feeding regimen on the time to establish full enteral feeding and incidence of NEC and other gastrointestinal complications in a group of SGA, IUGR infants identified by antenatal Doppler studies. [2]
| Materials and Methods | | |
ADEPT was a multicenter randomized controlled trial conducted in 54 hospitals in the United Kingdom and Ireland. The aim to evaluate the effects of an "early" enteral feeding regimen, starting milk feeds on day 2 after birth (between 24 and 48 hours of age) compared to one of "late" introduction of enteral feeds, starting feeds on day 6 after birth (between 120-143 hours of age) in a group of babies identified as being at high risk for NEC and milk intolerance by antenatal Doppler studies.
Population
Inclusion
- Gestational age up to and including 34 weeks + 6 days (dated by antenatal ultrasound or clinically)
- Antenatal ultrasound showing either
- Absent or reversed end diastolic flow velocities on at least 50% of the Doppler waveforms from the umbilical artery on at least one occasion during pregnancy
or
- Cerebral redistribution, defined as occurring when both the umbilical artery pulsatility index is greater than the 95 th centile and the middle cerebral artery pulsatility index is less than the 5 th centile for gestational age.
- Small for gestational age (birth weight <10 th centile for gestational age based on Child Growth Foundation Charts
- Postnatal age 20-48 hours.
Exclusion
- Major congenital abnormality including known chromosomal abnormality
- Twin-twin transfusion
- Intra-uterine transfusion or exchange transfusion
- Rhesus iso-immunisation
- Significant multi-organ failure prior to trial entry
- Inotropic drug support prior to trial entry
- Already received any enteral feeding
Intervention
Early feeding group
Feeding initiated between 24-48 hours after birth.
Late feeding group
Feeding initiated between 120-144 hours (5-6 days) after birth.
- Feeding increments were identical in both groups
- Feeds were gradually increased according to an "enteral prescription" tailored to birth weight, aiming to reach 150 mL/kg per day over 13 days in the smallest infants (<600 g) and 9 days in the largest infants (>1250 g)
- Mother's breast milk was recommended as the first choice of initial milk, followed by donor breast milk and infant formula
- Fortification of human milk was recommended once 150 mL/kg per day was reached, if additional nutrient support was required.
- Ventilation support or presence of umbilical catheters was not viewed as a contraindication to feeding.
Primary outcomes
- Age in days to achieve full enteral feeding of at least 150 mL/kg per day sustained for 72 hours.
- NEC (modified Bell's stage 1, 2, or 3).
Secondary outcomes
Death before hospital discharge; duration of hospital stay, intensive care, high-dependency care (defined in protocol), and parenteral nutrition; gastrointestinal perforation; gastrointestinal surgery; culture-positive sepsis; patent ductus arteriosus requiring treatment; cholestasis (conjugated bilirubin >25 μmol/liter); cranial ultrasound abnormality (ventricular dilatation ≥4 mm above 97 th centile, parenchymal hemorrhage or infarct, cystic periventricular leukomalacia); type of milk at discharge; and oxygen therapy, weight, and head circumference at 36 weeks' post-menstrual age and at discharge.
Allocation
A secure Web-based randomization service; hosted by the National Perinatal Epidemiology Unit Clinical Trials Unit.
A minimization algorithm was used to ensure a balanced allocation within hospital of recruitment, gestational age group (<29 weeks or ≥29 weeks), and type of Doppler abnormality (AREDFV or cerebral redistribution).
Blinding
- Masking clinicians to allocation was not possible
- A blinded committee reviewed all NEC and abdominal pathology forms, as well as any cases where there was uncertainty about the primary end point being met.
| Results | | |
- Four hundred four infants were recruited from April 2006 to May 2009 from 54 hospitals in the United Kingdom and Ireland
- Clinical characteristics at trial entry were well-balanced between groups, though there was a slightly higher proportion of infants >1250 g in the early group
- Feeding started within the specified time for 83% of infants in the early group and 76% infants in the late group
- First feed was exclusively human milk; 74% infants in the early group and for 91% of infants in the late group
- Full enteral feeding was reported in 95% of infants in each group.
Primary outcome
- Full feeds were achieved at an earlier age in the early group; median age was 18 days (interquartile range (IQR) 15-24) compared with 21 days (IQR19-27; HR: 1.36 (95% CI: 1.11-1.67); P =0.003) [Table 1]
- The number of episodes of all-stage NEC was 36 (18%) in the early group and 30 (15%) in the late group (relative risk (RR): 1.20 (95% CI: 0.77-1.87; P=0.42))
- The analysis was repeated adjusting for birth weight category becaus e there was a slight imbalance between groups, which could have explained some of the difference seen in feeding advancement. The adjusted HR was 1.45 (95% CI: 1.19-1.78; P, 0.001), which does not alter the conclusions of the main analysis
- The incidence of stages 2 and 3 NEC was 8% in both groups
- More infants in the early group had at least 1 episode of "abdominal pathology": 59 (29%) vs. 42 (21%; RR: 1.40 (95% CI: 1.00-1.98)), which was mainly due to a higher rate of dysmotility, meconium plug, and stage 1 NEC
- There was no significant difference in septic ileus, intestinal perforation, or surgery.
Secondary outcome
Late initiation of feeding was significantly associated with:
- More cholestatic jaundice
- Longer duration of parenteral nutrition
- Longer high dependency care
- Greater degree of postnatal growth restriction
There was no significant difference in culture positive sepsis, mortality, or overall length of hospital stay.
| Commentary | | |
This is the largest interventional study to date in this patient population, with IUGR related to antenatal AREDFV. This trial enrolled 402 preterm infants (mean GA was 31 weeks) with an increased risk of NEC. The risk was increased because they were growth-restricted and had abnormal antenatal Doppler.
The trial protocol used a slow feeding advancement (advance feeds by an average of 12 ml/kg/day).
This trial revealed no evidence of benefit in delaying the introduction of small volumes of enteral feeds in preterm, IUGR infants beyond 24 to 48 hours. Early introduction allows establishment of full feeds earlier with a reduction in cholestatic jaundice and improved weight gain. Delay in introducing feeds only caused morbidity, with no benefit.
This trial was included in a Cochrane review of 5 trials comparing early to delayed introduction of feeds in the preterm, also found no evidence of benefit of delaying the introduction of feeds. [3]
Abstracted from
Leaf A, Dorling J, Kempley S, McCormick K, Mannix P, Linsell L, Juszczak E, Brocklehurst P; Abnormal Doppler Enteral Prescription Trial Collaborative G: Early or delayed enteral feeding for preterm growth-restricted infants: A randomized trial. Pediatrics 2012;129(5):e1260-1268.
| References | | |
| 1. | Leaf A, Dorling J, Kempley S, McCormick K, Mannix P, Linsell L, et al. Abnormal doppler enteral prescription trial collaborative G: Early or delayed enteral feeding for preterm growth-restricted infants: A randomized trial. Pediatrics 2012;129:e1260-8. 
|
| 2. | Leaf A, Dorling J, Kempley S, McCormick K, Mannix P, Brocklehurst P. ADEPT - Abnormal Doppler Enteral Prescription Trial. BMC Pediatr 2009;9:63.
|
| 3. | Morgan J, Young L, McGuire W. Delayed introduction of progressive enteral feeds to prevent necrotising enterocolitis in very low birth weight infants. Cochrane Database Syst Rev 2011;3:CD001970.
|
[Table 1]
|
Search Pubmed for