Early Versus Late Initiation of Feeding in Preterm Newborns With Prenatal AREDF in Umbilical Artery (AREDF)

A Randomized Clinical Trial on Comparison of Early Versus Late Initiation of Feeding in Preterm Small for Gestation Infants Below 35 Weeks Gestation With Prenatal Absent or Reversal of End Diastolic Flow (AREDF) in Umbilical Artery

This research is being conducted in preterm newborns with 'in utero' growth restriction due to inadequate blood flow from the mother to the baby. These deprived babies adapt to the not so conducive uterine environment by certain adjustments in blood supply to internal organs thereby permitting as best as possible blood flow to brain heart etc., which are the vital organs and whose adequate functioning is required for survival. In this bargain the gut (intestines) gets poor blood supply and hence its appropriate functioning is jeopardized. In the past such babies (after birth) were not fed for days together which compromised their growth even further. Premature growth restricted' babies are at increased risk of further growth faltering if not fed in time as also to a condition called 'Necrotising enterocolitis' if fed liberally like other healthy neonates, characterized by abdominal distension, blood in stools and inability to feed for much longer duration thereby further affecting growth. This study is evaluating a feeding schedule of early versus late initiation of feeding to arrive at the best time to feed such doubly jeopardized premature growth restricted babies to avert the above mentioned consequences.

No study has been conducted in India to confirm the aforementioned fact and hence this study has been planned. The information learned from this study will help us to feed these small premature as well as growth restricted babies with AREDF better which will go a long way in the care of such preterm growth restricted newborns.

Study Overview

• Status: Completed
• Conditions: Time for Achievement of Full Feeds
• Intervention / Treatment: Other: Early Enteral feeding; Other: Late enteral feeding

Detailed Description

Absence or reversal of end diastolic flow (AREDF) in the umbilical artery is associated with poor outcome. This is further exaggerated by the presence of intrauterine growth retardation and oligohydramnios. Elective premature delivery of such fetuses is common. AREDF leads to circulatory redistribution with decreased blood flow to the lung, intestines, kidneys, skin, and muscle, and blood diverted to the brain, myocardium and adrenals. This reduction in visceral perfusion has been associated with an increased risk of necrotising enterocolitis, cerebral haemorrhage, and neonatal morbidity. Because of concern that feedings may increase the risk of necrotizing enterocolitis, some high-risk infants (most studies on preterm AGA) have received prolonged periods of parenteral nutrition without enteral feedings. Providing trophic feedings (small volume feedings given at the same rate for at least 5 days) during this period of parenteral nutrition was developed as a strategy to enhance feeding tolerance and decrease time to reach full feedings. Whether trophic feedings result in better outcomes than initially withholding feedings or providing progressively increasing feedings can be established only in proper clinical trials.

There are no standard guidelines to feed these preterm SGA infants born to mothers with abnormal antenatal Doppler studies. Furthermore, there are no randomized trials on feeding strategies in this group of neonates and hence we planned to carry out this study on comparison of early versus delayed initiation of feeding in preterm SGA infants with AREDF.

The purpose of this study is to compare the time to reach full enteral feeds, time to regain birth weight etc. in babies who are fed carefully versus those who are not fed for the initial days. It is postulated that early gut priming may stimulate the gut to secrete certain trophic and growth factors which may make it better able to tolerate enteral feeds improving the overall growth and also reducing chances of infection.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 days and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Preterm neonates below 35 weeks gestation born at the study center(s)
2. Small for gestational age (SGA) ie weight < 10th centile for gestation
3. Absent or reverse end diastolic flow (AREDF) in umbilical artery'

Exclusion Criteria:

1. Babies with major congenital malformations.
2. Babies with severe asphyxia as defined by apgar score <4 at 5 min of life with cord/within one hour of life pH< 7.0.
3. Shock requiring pressor support at the time of randomization.
4. Babies born with gastrointestinal surgical conditions precluding enteral feeding.
5. Babies with abdominal distension, bilious or hemorrhagic aspirates or recurrent vomiting at the time of randomization.
6. Refusal to obtain consent.
7. Gestation below 26 weeks.
8. Hydrops fetalis.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early enteral feeding; Early enteral feeding group received minimal enteral feed (MEF) of 8 ml/kg of expressed human milk of the biologic mother for 48 hours followed by regular feeding with feed increments of 20ml/kg/day to reach 150 ml/kg.	Other: Early Enteral feeding; Feeding with expressed breast milk @ 8ml/kg/day for 48 hrs after randomization at 60+/-12 hrs of life
Active Comparator: Late enteral feeding; Late enteral feeding group was kept NPO for a period of 48 hours followed by minimal enteral feed (MEF) of 8 ml/kg of expressed human milk of the biologic mother for 48 hours and thereafter received regular feeding with feed increments of 20ml/kg/day till full enteral feeds of 150 ml/kg/day were achieved	Other: Late enteral feeding; Nil per oral for another 48 hrs after randomization at 60+/-12 hrs of life followed by Feeding with expressed breast milk @ 8ml/kg/day for 48 hrs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time taken to achieve full feeds	First day of the three days when full enteral feeding of 150 ml/kg has been achieved and sustained as recorded from the nursing chart of the infant.	in days upto six weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Days to regain birth weight	After the initial fall in weight the first day when birth weight is regained or crossed and the value remains above the birth weight for subsequent 2 days will be recorded as day of life birth weight has been regained.	in days upto six weeks
Feed intolerance	Feed intolerance was measured as number of episodes of any of the following symptoms per infant till he/she reached full feeds of 150ml/kg and sustained it for 2 days.; bilious or hemorrhagic aspirates( irrespective of the volume),; vomiting ( >2 times in 12 hours duration) and; clear or milky aspirate >50% of the previous feed volume necessitating feed stoppage for 24 hours	till achievement of full feeds
duration of stay	This was taken to be the interval between birth and the day the newborn was discharged home.	in days upto twelve weeks

Collaborators and Investigators

• Sponsor: Lady Hardinge Medical College
• Collaborators: All India Institute of Medical Sciences, New Delhi
• Investigators: Principal Investigator: Sushma Nangia, MD, DM, All India Institute of Medical Sciences, New Delhi

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): April 1, 2007

Study Registration Dates

• First Submitted: December 23, 2012
• First Submitted That Met QC Criteria: December 31, 2012
• First Posted (Estimate): January 3, 2013

Study Record Updates

• Last Update Posted (Estimate): January 3, 2013
• Last Update Submitted That Met QC Criteria: December 31, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Preterm; Necrotizing enterocolitis; SGA; AREDF; Early feeding; Late feeding; Feed intolerence
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: AIIMS/06/AREDF