We appreciate the readers’ interest in our
study [1], and provide the clarifications:
i)
The neonates
were approached for randomization within first 96 hours and were
enrolled as soon as the participants were deemed fit for
inclusion. However, we did not record exact time of
randomization or initiation of feeding.
ii) We agree with the point about
subgroup analysis based upon weight and small for gestational
age status. Detailed analysis shall be published later. There
was no difference in time to reach full enteral feed,
hypoglycemia, feed intolerance or necrotizing enterocolitis
(NEC) among small for gestational age (SGA) neonates too (Table
I). This finding is reassuring and indicates the
applicability of trial to growth restricted neonates which are
considered at higher risk for adverse outcomes. The SGA neonates
were overall at significantly higher risk for NEC (7 vs 2; P-0.016)
as compared to appropriate for gestational age, irrespective of
feeding schedule.
Table I Comparison of Primary and Secondary Outcomes as per Appropriateness for Gestational Age
|
Outcomes |
Two-hourly |
Three-hourly
|
|
|
group |
group |
|
(n=110) |
(n=99)
|
|
Appropriate for gestational age |
|
|
|
Time to reach full enteral feeds
(n=100)a |
5.27(1.73) |
4.90(1.17)
|
|
Hypoglycemia |
4(3.64)
|
3(2.97) |
|
Episodes of feed intolerance |
8(7.27) |
5(5.1) |
|
Necrotising enterocolitis |
0 |
2(1.98) |
|
Small for gestational age |
|
|
|
Time to reach full enteral feeds
(d)a |
5(1.49) |
5.36(2.09) |
|
Hypoglycemia |
2(3.08) |
4(5.41) |
|
Episodes of feed intolerance |
5(7.69) |
7(9.46) |
|
Necrotising enterocolitis |
4(6.15) |
3(4.05)
|
|
Values in no. (%) except amean
(SD). All P values >0.05. |
iii) We agree with the point raised over
excluding neonates with absent or reversed end diastolic flow
(A/REDF). However, at the time of commencement of the study
(2017) our unit policy was withholding feeds for first 24 hours
and thereafter slow advancement of feeds (10-20 mL/kg/day) in
neonates with A/REDF [2]. For the index study we planned rapid
advancement of feeds (30 mL/kg/day) for all enrolled infants and
the team was worried over the rapid advancement of feeds in
A/REDF population. Therefore, inclusion of neonates with A/REDF
would have either led to deviation from the protocol. Also, as
of now, three-hourly feeding is not a standard of care.
Therefore, to ensure uniformity in study protocol and to ensure
safety we excluded neonates with A/REDF. We are also aware of
the Cochrane review published in 2017 (after commencement of our
study) showing no evidence of increase in NEC with rapid
advancement of feed in these neonates [3].
iv) We agree that it is an important
outcome. However, we did not objectively record this data.
v) None of the neonates in the study
received probiotics.
vi) Due to high volume of admissions and
rapid turnover we did not record time to reach full oral feeds
and the duration of the transition in neonates who were on tube
feeds at enrolment. However, as per our policy the spoon feeds
are started at 31 weeks of postmenstrual age.
REFERENCES
1. Yadav A, Siddiqui N, Debata PK. Two-hourly
versus three-hourly feeding in very low birthweight neonates: A
randomized controlled trial. Indian Pediatr. 2021;58:320-4.
2. Dutta S, Singh B, Chessell L, et al.
Guidelines for Feeding Very Low Birth Weight. Infants Nutrients.
2015;7:423-42.
3. Oddie SJ, Young L, McGuire W. Slow advancement of enteral
feed volumes to prevent necrotizing enterocolitis in very low
birth weight infants. Cochrane Database Systematic Reviews.
2017;8:CD001241.
