early versus late feeding in the newborns with REDF/AEDF Neonates

1. Early versus Late Enteral Feeding in Preterm
Intrauterine Growth Restricted Neonates with
Antenatal Doppler Abnormalities: An Open-Label
Randomized Trial
Moderator Dr Shruthi
Presentor- Dr Hamsa K N

2. • Vishal Vishnu Tewari, Sachin Kumar Dubey,
Department of Pediatrics, Army Hospital (Referral &
Research), New Delhi
• Reema Kumar, Shakti Vardhan,C. M. Department of
Obstetrics & Gynecology, Army Hospital (Referral &
Research), New Delhi
• Sreedhar, Department of Radiodiagnosis, Army
Hospital (Referral & Research), New Delhi
• Girish Gupta, Department of Pediatrics, INHS
Sanjeevani, Cochin

3. Introduction
• The incidence of lowbirth-weight IUGR in India is 21% with the
majority of the cases attributable to feto-maternal environment
and of a non-genetic etiology .
• A subset of this IUGR population is identified antenatally to have
abnormal umbilical artery (UA) Doppler flow velocities
predisposing them to necrotizing enterocolitis (NEC) .

4. • Absent or reversed end diastolic flow (AREDF) on
Umbilical Artery Doppler flow velocity assessment is a
reflection of the fetal ‘cerebralization of blood flow’
seen in chronic fetal hypoxia and is associated with
increased risk of adverse perinatal outcomes
• A combination of direct hypoxic-ischemic mucosal
injury, susceptibility to stasis and prolonged ileus,
abnormal development of gut microbiome with
bacterial transmigration contribute to the increased
incidence of NEC .

5. • Abnormalities in placenta and increased placental vascular
resistance are common in IUGR
• Fetus with IUGR shows abnormality in the Umbilical Doppler
flow velocities secondary to adaptive hemodynamic changes in
the fetal circulation.
• Fetal hypoxia and fetal hypercarbia causes cerebral vasodilatation
and increased peripheral vascular resistance.
• Increased in mesenteric vascular resistance – reduced intestinal
perfusion and hypoxic injury to gut

6. • Redistribution of blood to vital organs results in
Reduced Diastolic Flow in the Fatal Umbilical
Arteries- leading to absent or reversal of end
diastolic flow
• Abnormality on motor, secretory and mucosal
function of the intestine making intestine vulnerable
to stasis and abnormal colonization.

7. Objective
• To study early versus late feeding in preterm IUGR
neonates for time required to attain sufficient feed
volume to discontinue PN and increased risk of
NEC or feed intolerance.

8. Method
• Type of study -single-centre open-label randomized trial
• Study period- from 1 January 2014 to 31 July 2015 18 Months
• Sample size- 62, calculated by keeping incidence of preterms
based on fesibility of previous studies and with alpha value of 5%
and power of 80 %
• Doppler was used as the primary surveillance tool in the fetus.
• When UA Doppler flow indices were normal, it was repeated
every 14 days but if they were abnormal and delivery was not
indicated, daily surveillance was performed.

9. • Ductus venosus (DV) Doppler was used for timing of
delivery.
• In the preterm IUGR fetus with AREDF on UA
Doppler detected before 32 weeks of gestation, delivery
was recommended when DV Doppler became abnormal
or umbilical venous (UV) pulsations appeared.
• Delivery was considered by 32 weeks of gestation with
AREDF even when DV Doppler was normal.

10. • Antenatal steroids use in these mothers was universal
• NICU practices included early aggressive PN through placement
of UV catheters or peripherally inserted central catheters (PICC),
weaning of PN once the enteral intake reached 120ml/kg/day in
extreme preterm and 110ml/kg/day in very preterm, use of
exclusive breast milk feeding with mothers’ own milk or donor
breast milk and complete avoidance of formula milk and routine
use of human milk fortifier.

11. • Full feeds were defined as daily enteral feed volumes of
150–180ml/kg/day, which allowed consistent weight gain
for 3 successive days.
• Mothers were encouraged to express breast milk and
assistance was provided to them

12. Inclusion Criteria
• Intramural preterm IUGR neonates32 weeks with
AREDF on UA Doppler
• Birth weight below the 10th centile for the
gestational age
• After obtaining written informed consent from the
parents.

13. Exclusion criteria
• The following neonates were excluded
who were extramural-
• Symmetric IUGR
• Antenatally suspected intestinal anomaly, lethal congenital
anomaly, dysmorphic, needed invasive ventilation
• Inotropic support or extensive resuscitation and parent
unavailable.
• Intramural preterm IUGR neonates<27 weeks

14. Randomization
• Serially admitted preterm IUGR neonates32 weeks eligible for the
study were enrolled and stratified as extreme preterm (27–29
weeks 6 days) or very preterm (30–32 weeks 6 days).
• Following initial stabilization by 12h of age, babies were
randomized to early feeding or late feeding
• Babies were randomised to early feeding and late feeding arm
using online service

15. • Random permuted blocks of varying sizes
with allocation ratio of of 1:1 generated.
• Serially numbered opaque sealed envelopes
were used to conceal allocation

17. Intervention
• Intervention Early feeding was defined as initiation of
expressed breast milk (EBM) feeding within 12–48 h after
birth
• Late feeding was defined as initiation of feeds by 120–144 h
after birth or later.

18. • Minimal enteral nutrition (MEN) with EBM was
given in all cases and continued for 48–72 h.
• Feed progression using EBM was done at the rate of 10–
15 ml/kg/ day as per a feed advancement protocol (FAP)
to achieve a stable, enterally tolerated volume of 150– 180
ml/kg/day.

21. Monitoring
• Initiation of feeding was done using a combination of clinical
parameters, included abdomen appearance and feel, meconium
passage, color and nature of oro gastric aspirate, bowel sounds, hand-
to mouth behavior of baby and bowel gas pattern on abdominal
radiograph.
• These were scored from 0 to 2.
• A total score of 3 allowed feed initiation, while a score of 4 required
deferment of feed initiation and reassessment every 4 h till the total
score permitted feed initiation.
• NEC was diagnosed as per Modified Bells staging.
• FI was monitored by abdominal girth measurement, pre feed gastric
aspirate volume and color, vomiting and radiograph of abdomen

22. • NEC was diagnosed as per Modified Bells staging.
• FI was monitored by abdominal girth measurement, pre feed gastric
aspirate volume and color, vomiting and radiograph of abdomen

24. Feeding and action
Parameter
Significant feeding Action
Abdominal girth >2cm increase over
baseline in 24 hour
With hold feeding
Pre- feed aspirate volume >50% of feed volume(to
be checked after 3 feeds)
With hold feeding and
evaluate for NEC/ sepsis
Pre feed aspirate volume Bilious/ altered or fresh
blood
Wit hold feeding and
evaluated for NEC/ sepsis
Vomiting > 1 volume with yellow or
green colour and or altered
blood
With hold feeding and
evaluate for NEC/ sepsis

25. • Primary outcome:
Time in days required to attain an enteral feeding
volume sufficient to allow discontinuation of PN fluids
and incidence of NEC.

26. • Secondary outcome:
1. Incidence of FI
2. Time to attainment of full feeds
3. Time to regain birth weight
4. Incidence of LOS
5. Duration of hospital stay and cause mortality

28. Results
• 77 neonates were eligible for inclusion of which 15 were
excluded for various reasons .
• 62 neonates were enrolled and stratified as extreme grouped
preterm or very preterm .
• Ten extreme preterm were randomized to early feeding and an
equal number received late feeding, while in the very preterm
population equal numbers of 21 neonates were randomized to
receive early and late feeding.
• Babies in both the groups had similar baseline characteristics and
showed no statistically significant differences.

29. • The median duration was shorter in the early feeding arm of
both the groups by 4 days. There was no significant difference in
the incidence of NEC or FI or combined outcome of NEC and
FI in the extreme preterm and the very preterm
• Full feeds were achieved faster in the early feeding arm of both
the groups

30. Limitations of study
• Small number of extreme preterm neonates.
• Study doesn’t give effects regarding the rate of
increase of feeds.

31. Strengths of study
• Faster attainment of full feeding in early feeding doest
show any increase in incidence of NEC
• Earlier regaining of birth weight in early feeding
group.
• Usage of Exclusive Breast Milk.

32. • Study shows early feeding in preterm IUGR neonates with
AREDF using exclusive breast milk as per a standardized
feeding initiation and advancement plan does not increase
the risk of NEC or FI.
• The study demonstrates discontinuation of PN at enteral
feed volumes lower than conventionally accepted is well
tolerated by pre terms and results in an overall low
incidence of sepsis

33. Similar studies
• Study by Jessie Morgan, Lauren Young, William
McGuire Delayed introduction of progressive
enteral feeds to prevent necrotising enterocolitis
in very low birth weight infants- trials defined
delayed introduction of progressive enteral feeds
later than four to seven days after birth and early
introduction as four days or less after birth did not
detect statistically significant effects on the risk of
NEC.

34. • Study by Abishek Somashekar Aradhya, Kanya
Mukhopadhyay et al. Feed intolerance in preterm neonates
with antenatal reverse and diastolic flow in UA: A
retrospective study – Ealy enteral feeding as early as 24
hours can be initiated in REDF if there is nno abdominal
symptoms and signs
• Study by M.F Ahmed , Dar Peer et al. Early feeding
tolerance in smll for gestational age infants with normal
versus abnormal antenatal Doppler characteristics- early
feeding is not associated with higher risk of NEC

37. Thank you

38. Next class by Pravalli Vanama-
Case Presentation