OPTIMAL FEEDING OF LOW

BIRTH WEIGHT INFANTS

Standard Treatment Guidelines

Neonatal Guideline Development Group

(Secretariat: Department of Pediatrics, AIIMS)
 TABLE OF CONTENTS
Executive summary ..................................................................... 1

Introduction................................................................................ 5

Methodology ............................................................................... 8

Recommendations ...................................................................... 22

Implementation tools .................................................................. 27

Bibliography ..............................................................................29
 FOREWORD
To be developed
Executive summary
Low birth weight (LBW) is defined as weight less than 2500g at birth. The World
Health Organization estimates that 16% of allneonates—nearly 20 million—are born
low birth weight(birth weight less than 2500 g) every year. In India, nearly one-
third of live born babies are low birthweight—8 million every year. These neonates
are at 11–13times increased risk of dying as compared to normal birthweight
babies.

Low birth weight neonates may be gestation-wiseimmature (i.e. preterm) or may

have sufferedintrauterine growth restriction (IUGR). The incidence of prematurity is
fairlyconstant at 8–16% throughout the world. But the prevalence of IUGR varies
widely – in South Asia, IUGR is responsiblefor two-thirds of LBW neonates.

LBW infants are at risk of short and long term morbidities. Short term morbidities
include hypothermia, hypoglycemia, increased risk of sepsis and feeding difficulties
among others. Feeding difficulties in LBW infants are often due to poor feeding
skills because of prematurity per se, altered perfusion of the gut due to high
resistance in uterine and umbilical arteries while in utero, and also due to non-
availability of own mother’s milk in adequate volume in the initial few days after
birth. Providing optimal nutrition not only improves growth but also results in
better neurodevelopmental outcome in these infants.

Optimal nutrition to LBW infants can be provided by parenteral or enteral means.

While parenteral nutrition is essential when the infant is critically ill, enteral route is
preferred over parenteral route once the infant is stabilized because of the cost and
inherent risks involved with parenteral nutrition. Enteral feeding should be initiated
and advanced as early as possible in LBW infants to optimize nutrition.

The objective of this standard treatment guidelines is to improve the quality of care
received by LBW infants inhealth facilities of India through improved capacity of
health care providers. These guidelines focus on optimal feeding of clinically stable
LBW infants in India. They do not specificallyaddress the feeding of infants with a
birth weight less than 1.0 kg (known as extremely LBW, ELBW),who are often
clinically unstable and may require parenteral nutrition. Health care providers can
adapt the recommendations to their setting and implement to improve short- and
long-term outcomes of LBW infants.
1
 The Guideline Development Group (GDG)searched the existing guidelines on
feeding of low birth weight infants using a broad search strategy. After comparing
the available guidelines using the standard approach, the GDG decided to use the
WHO optimal feeding of LBW guidelines as the base for the present guidelines and
adopt it using the National Neonatology Forum (NNF) guidelines.

The WHO guidelines had enlisted 18 priority research questions. The GDG identified
eight additional RQs from the NNF practice guidelines, of which four were
considered to be relevant and important for the present guidelines. In addition, the
group conducted an electronic survey followed by telephonic discussion among
healthcare providers from secondary level facilities to identify additional research
questions.

The GDG finalized the recommendations by adopting or adapting the original

recommendations from the WHO and NNF guidelines:

Recommendations on optimal feeding of low birth weight infants

Recommendation Adopted/adapted
from
What to feed: Choice of milk

Low birth weight (LBW) infants, including those with very low Adopted from the WHO
birth weight (VLBW), should be fed mother’s own milk. guidelines
LBW infants, including those with VLBW, who do not have access Adapted from the WHO
to mother's own milk/ whose mother's own milk is guidelines
insufficient,should be fed donor human milk.
LBW infants, including those with VLBW, who cannot be fed Adopted from the WHO
mother's own milk or donor human milk should be fed standard guidelines
infant formula.
VLBW infants who cannot be fed mother's own milk or donor
human milk should be given preterm infant formula if they fail to
gain weight despite adequate feeding with standard infant
formula.
VLBW infants who are fed mother’s own milk or donor human milk Adopted from the WHO
should not routinely be given bovine milk-based human milk guidelines
fortifier.
VLBW infants who fail to gain weight despite adequate breastmilk
feeding should be given human-milk fortifiers, preferably those
that are human milk based.
What to feed: Supplements

2
LBW infants (1500-2499 g) should be given vitamin D Adapted from the WHO
supplements at a dose of 400 IU per day until 6 months of age. and NNF guidelines
VLBW infants (<1500 g) should be given vitamin D supplements
at a dose of 800 IU per day until 6 months of age.
VLBW infants who are fed mother’s own milk or donor human milk Adapted from the WHO
should be given daily calcium (120-140 mg/kg per day) and guidelines
phosphorus (60-90 mg/kg per day) supplementation until term
gestation (40 weeks’ postmenstrual age).
VLBW infants fed mother’s own milk or donor human milk should Adapted from the WHO
be given 2-4 mg/kg per day iron supplementation starting at 2 and NNF guidelines
weeks until 6 months of age.
Other LBW infants (1500-2499 g) fed mother’s own milk or donor
milk should be given 2-3 mg/kg per day iron starting at 6-8
weeks until 6 months of age.
Routine zinc supplementation for LBW infants who are fed Adopted from the WHO
mother's own milk or donor human milk is not recommended at guidelines
the present time, because there is not enough evidence of
benefits to support such a recommendation.
When to initiate feeding?

LBW infants (birth weight > 1200 g)who are able to breastfeed Adopted from the WHO
should be put to the breast as soon as possible after birth when guidelines
they are clinically stable.
LBW infants with birth weight <1200 g should be given 10 mL/kg Adapted from the WHO
per day of enteral feeds, preferably expressed breast milk, guidelines
starting from the first day of life, with the remaining fluid
requirement met by intravenous fluids.
How to feed?

LBW infants who need to be fed by an alternative oral feeding Adopted from the WHO
method should be fed by cup (or palladai, which is a cup with a guidelines
beak) or spoon.
VLBW infants requiring intragastric tube feeding should be given Adopted from the WHO
bolus intermittent feeds. guidelines
In VLBW infants who need to be given intragastric tube feeding, Adopted from the WHO
the intragastric tube may be placed either by oral or nasal route, guidelines
depending upon the preferences of health-care providers.
VLBW infants on intragastric tube feeding should be fed 2 hourly. Adapted from the NNF
Other LBW infants (1500-2499 g) on intragastric tube feeding guidelines
should be fed 3-hourly.
LBW infants who are fully or mostly fed by an alternative oral Adopted from the WHO
feeding method should be fed based on infants’ hunger cues, guidelines
except when the infant remains asleep beyond 3 hours since the
last feed.
3
How much to feed?

LBW infants with birth weight >=1200 g should be initiated on Adapted from the NNF
60-80 mL/kg per day of enteral feeds, preferably expressed guidelines
breast milk, on the first day of life.
In VLBW infants who need to be fed by an alternative oral feeding Adopted from the WHO
method or given intragastric tube feeds, feed volumes can be guidelines
increased by up to 30 ml/kg per day with careful monitoring for
feed intolerance.
LBW infants who need to be fed by an alternative oral feeding Adapted from the NNF
method or given intragastric tube feeds, should be fed up to 180- guidelines
200 mL/kg per day after 1-2 weeks of life.
Optimal duration of exclusive breastfeeding

LBW infants should be exclusively breastfed until 6 months of Adopted from the WHO
age. guidelines
Miscellaneous issues

Non-nutritive sucking (NNS) is recommended in VLBW infants on Adapted from the NNF
intragastric tube feeding to improve transition from gavage to guidelines
breast feeding.
Growth monitoring

LBW infants should be monitored for optimal growth by serial Adapted from the NNF
weight and head circumference measurement at least once guidelines
weekly in the first weeks of life, using an appropriate growth
chart like Fenton’s chart.

4
Introduction
Low birth weight (LBW) is defined as weight less than 2500g at birth. The World
Health Organization estimates that 16% of allneonates—nearly 20 million—are born
low birth weight(birth weight less than 2500 g) every year. The highest burdenof
low birth weight (LBW) neonates is in South Asia, wherean estimated 31%
neonates are born low birth weightcontributing to nearly one half of the global
burden.In India, nearly one-third of live born babies are low birthweight—8 million
every year. These neonates are at 11–13times increased risk of dying as compared
to normal birthweight babies and are also predisposed to a variety of adult
onsetdiseases.

Low birth weight neonates may be gestation-wiseimmature (i.e. preterm) or may

have sufferedintrauterine growth restriction (IUGR). The incidence of prematurity is
fairlyconstant at 8–16% throughout the world. But the prevalence of IUGR varies
widely – in South Asia, IUGR is responsiblefor two-thirds of LBW neonates.LBW
infants are also classified as very low birth weight (VLBW) if their birth weight is
less than 1.5 kg, and as extremely low birth weight (ELBW) if their birth weight is
less than 1 kg. All these infants have a higher mortality risk than infants who do
not have LBW.

LBW infants are at risk of short and long term morbidities. Short term morbidities
include hypothermia, hypoglycemia, increased risk of sepsis and feeding difficulties
among others. Feeding difficulties in LBW infants are often due to poor feeding
skills because of prematurity per se, altered perfusion of the gut due to high
resistance in uterine and umbilical arteries while in utero, and also due to non-
availability of own mother’s milk in adequate volume in the initial few days after
birth. Providing optimal nutrition not only improves growth but also results in
better neurodevelopmental outcome in these infants.

Optimal nutrition to LBW infants can be provided by parenteral or enteral means.

Even though parenteral nutrition is essential when the infant is critically ill, enteral
route is preferred over parenteral once the infant is stabilized because of the cost
and inherent risks involved with parenteral nutrition. Enteral feeding should be
initiated and advanced as early as possible in LBW infants to optimize nutrition.

5
However, LBW feeding is fraught with controversies resulting in wide variations in
clinical practice.

Formulating a standard feeding guidelines based on current best evidence would

help to streamline enteral feeding practices in LBW infants. Health care providers
can adapt the recommendations to their setting and implement to improve short
term outcomes of LBW infants.

Guideline Development Group (GDG)

The following experts were involved in the development of these guidelines: Vinod
Paul (AIIMS, New Delhi), Ashok Deorari (AIIMS, New Delhi), M Jeeva Sankar
(AIIMS, New Delhi), Ruchi Nanavati (KEM, Mumbai), Jayashree Mondkar (LTMMC,
Sion, Mumbai), Ramesh Agarwal (AIIMS, New Delhi), Nandkishore Kabra (AIIMS,
New Delhi), Ashish Jain (MAMC, Delhi), and N Chandrakumar (AIIMS, New Delhi).

Team from NHSRC, NICE, (NHSRC team to fill the names and their roles)

The guideline development group (GDG) met once in September 2015 to deliberate
on the steps and timelines. A working group comprising three members of the GDG
(MJS, NC, and RN) developed the draft guidelines based on the agreed plan.
Thisdraft was reviewed electronically and approved by the other GDG members.

Declaration of interests

All the members of the GDG declare no conflict of interest.

Funding source

National Health Systems Resource Center (NHSRC), New Delhi

Scheduled review

We plan to update the STG every 3 years.

Scope of the guidelines

Target audience

The primary audience for these guidelines is intended to be healthcare workers in

primary and secondary level health facilities as well as referral hospitals. The
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guidelines are also expected to be used by policy-makers, program managers, and
health facility managers to set up a system for optimal care of LBW infants.

Further, many of the recommendations will be relevant for community health

workers providing care to LBW infants at home. The information in these guidelines
will be included in several capacity strengthening courses for health workers, such
as for Essential Newborn Care and Integrated Management of Newborn and
Childhood Illness (IMNCI), and in community health worker training on caring for
the newborn at home.

Population of interest

The guidelines focus on the feeding of clinically stable LBW infants being cared for
in a health facility or at home. Some of the recommendations focus only on very
low birth weight infants (VLBW; birth weight less than 1.5 kg). The guidelines do
not specifically address the feeding of infants with a birth weight less than 1.0 kg
(extremely low birth weight; ELBW), who are often clinically unstable and may
require parenteral nutrition. Further, the guidelines do not provide separate
recommendations for the two groups of LBW infants – term small-for-gestational
age (SGA) and preterm – because of lack of evidence.

Critical outcomes

Four outcomes were considered to be critical by the GDG: mortality, severe

morbidity, neurodevelopment, and anthropometric status. Mortality and severe
morbidity over the short term (e.g. during initial hospital stay after birth) or long
term (e.g. infant mortality) were considered to be critical. Neurodevelopment and
anthropometric status were considered critical only if measured at age 6 months or
more.

Benefits and harms in critical outcomes formed the basis of the recommendations.
When information on critical outcomes was not available, other non-critical
outcomes were considered. Examples of these other outcomes include
breastfeeding duration or exclusivity, short-term growth, duration of hospital stay,
hemoglobin levels and bone mineralization.

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Methodology
Step 1: Search and select guidelines

The GDG searched the electronic database MEDLINE via PubMed and the websites
www.who.int (World Health Organization), http://www.guideline.gov (National
Guideline Clearing House of US), http://www.nice.org.uk (National Institute for
Clinical & Care Excellence, UK), www.aap.org (American Academy of Pediatrics),
www.cps.ca(Canadian Pediatric Society), and www.nnfi.org (National Neonatology
Forum, India) to search for existing guidelines on feeding of low birth weight
infants.

The following search strategy “(feeding[All Fields] AND ("infant, low birth
weight"[MeSH Terms] OR ("infant"[All Fields] AND "low"[All Fields] AND "birth"[All
Fields] AND "weight"[All Fields]) OR "low birth weight infant"[All Fields] OR
("low"[All Fields] AND "birth"[All Fields] AND "weight"[All Fields] AND "infants"[All
Fields]) OR "low birth weight infants"[All Fields])) AND Guideline[ptyp]” was used
for searching PubMed. A similar search strategy was used to search the websites of
national and international organizations.

Two relevant citations – one each by the World Health Organization and Chinese
Society of Parenteral and Enteral Nutrition (CSPEN) – were identified. In addition,
the GDG identified another guideline – by National Neonatology Forum, India –by
hand searching. Another review-cum-guidelines – published recently in 2015 – by
an expert group from McMaster University, Canada was also identified by hand
searching.

Step 2: Compare and sift guidelines

Table 1 depicts the key features of the three guidelines (WHO, CSPEN, and NNF).

Of the three guidelines, only one – by the World Health Organization – has been
evaluated thoroughly by the National Guideline Clearinghouse of the US
(www.guideline.gov). The technical quality and the process of development of the
other two guidelineswere evaluated by two members of the GDG using the AGREE-
GRS instrument (http://www.agreetrust.org/).

8
Both the guidelines scored3 to 5 in the 7-point scale for individual items (lowest
quality being 1). On the overall guideline assessment, one guideline (CSPEN)
scored 2 while the NNF guidelines scored 6 (strongly disagree=1; strongly agree=7
in a 7-point scale).

The GDGunanimously decided to use the WHO feeding guidelines as the base for
the present guidelines and adopt it using the NNF guidelines, if there was a need to
adopt the recommendations to Indian context.

9
 Table 1: Comparison of guidelines
Guideline Title Guidelines on optimal feeding of low CSPEN guidelines for NNF Clinical Practice Guidelines
birth-weight infants in low- and- nutrition support in
middle income countries neonates
Date Released 2011 2013 2010
Adaptation Not applicable: The guideline was not Not applicable Not applicable
adapted from another source.
Guideline World Health Organization (WHO) - Chinese Society of National Neonatology Forum, India
Developer(s) International Agency Parenteral and Enteral
Nutrition, Chinese Society of
Pediatrics
Source(s) of Funding These guidelines were developed using ? None National Neonatology Forum, India
funding to the Department of Maternal,
Newborn, Child and Adolescent Health
from the United States Agency for
International Development.
Financial None of the members of the Guideline None declared any conflict Not clear
Disclosures/Conflicts Development Group (GDG) declared any of interest.
of Interest conflicts of interest.
Disease/Condition(s) • Low birth weight (LBW) (<2.5 kg) Neonates LBW neonates
• Very low birth weight (VLBW) (1.0 to NOT restricted to LBW (one section in the document is on
1.5 kg) neonates ‘Feeding of LBW Infants’)
Intended Users Advanced Practice Nurses Not mentioned Not mentioned
Allied Health Personnel
Dietitians
Health Care Providers
Health Plans
Hospitals
Managed Care Organizations
Nurses
Physician Assistants
Physicians
Public Health Departments
Guideline To improve the quality of care received To provide proposed To have Neonatal practice Guidelines
Objective(s) by low birth weight (LBW) infants in advisable ranges for nutrient which are evidence based relevant to
 developing countries through improved intakes in neonates India, acceptable to local needs and
capacity of health workers who care for developed by a large group with
these infants wider representation
Target Population Clinically stable low birth weight (LBW)* All neonates including All neonates
infants in low- and middle-income preterm and most sick term
countries, including infants born at term neonates
(after 37 and before 42 completed
weeks of gestation) and preterm (born
up to 37 completed weeks of gestation)
*Weighing between 1.0 and 2.5 kg at
birth
Note: The recommendations do not
specifically address the feeding of infants
with a birth weight less than 1.0 kg
(known as extremely LBW, ELBW), who
are often clinically unstable and may
require parenteral nutrition.
Major Outcomes • Mortality Not clear Not clear
Considered • Severe morbidity
• Neurodevelopment
• Anthropometric status
Cost Analysis Yes No No
Performed/Reviewed
?
Methods Used to Hand-searches of Published Literature Based on the ‘considered A search of medical literature using
Collect/Select the (Primary Sources) review of available scientific specific search terms was made using
Evidence Hand-searches of Published Literature reports on the subject, and PubMed, Medline, Cochrane trial
(Secondary Sources) on expert consensus for register, Google Scholar and ‘Ovid’.
Searches of Electronic Databases which the available scientific Abstracts of the retrieved studies
data are considered were inspected and selected studies
inadequate’ were perused in detail and relevant
Further details not available data extracted.
This search was conducted
independently by the three authors in
each group and the references were
subsequently pooled to widen the

11
 reference base.
Description of Search Strategy Not mentioned A search of medical literature using
Methods Used to A series of systematic reviews were specific search terms was made using
Collect/Select the conducted and published by the World PubMed, Medline, Cochrane trial
Evidence Health Organization (WHO) as Optimal register, Google Scholar and ‘Ovid’.
feeding of low-birth-weight infants: In addition, relevant cross-references
technical review in 2006. The databases were looked at in detail. Abstracts of
searched included the Cochrane conference proceedings of National
Database of Systematic Reviews of and International meetings (NNF,
randomized controlled trials (RCTs), the IAP, PAS, ESPR) and
Cochrane Controlled Trials Register, the recommendations of various
Cochrane Database of Abstracts of professional bodies were also
Reviews of Effectiveness (DARE), the reviewed. A hand search of MD & DM
Cochrane neonatal collaborative review dissertations and non-indexed
group specialized register, MEDLINE journals like Journal of Neonatology
(1966 to 2005), and EMBASE (1966 to was performed.
2005). The reference lists of relevant
articles and a number of key journals
were hand searched. Every effort was
made to include relevant non-English
language articles and abstracts. This
approach was complemented by an
additional search in August-September
2010 to identify relevant research
papers published between January 2005
and August 2010. The first set of search
terms ("all fields" and "MESH terms")
was related to the population of interest:
low-birth-weight (LBW) infant, preterm
infant, premature infant, SGA infant,
fetal growth retardation, intrauterine
growth retardation, intrauterine growth
restriction. The studies identified also
needed to have at least one of the
search terms in the second set related to
issues in feeding of LBW infants. The

12
 second set of search terms included:
feeding, enteral nutrition, breastfeeding,
breast milk, human milk, donor milk,
formula, human-milk fortifier, vitamin,
micronutrient, vitamin A, vitamin D,
calcium, phosphorus, zinc, iron, cup,
bottle, spoon, tube, feeding tolerance,
trophic feeding, minimal enteral nutrition
and gut priming.
Methods Used to Weighting According to a Rating Scheme The quality and strength of Literature was assessed for
Assess the Quality (Scheme Given) the supporting literature appropriateness of study design,
and Strength of the was graded according to limitations in employed study design,
Evidence American Society for and inconsistency across different
Parenteral and studies, and applicability to Indian
Enteral Nutrition (ASPEN). neonates. Evidence provided by
The grade of individual studies was classified as
recommendation depends per standard recommendations.
on the scientific quality of Based on evidence guidelines are
the studies reported. Meta- provided for practice and research
analyses were used to issues.
organize information and to
draw conclusions about
overall treatment effect
from multiple studies on a
particular subject.
Rating Scheme for Quality of the Evidence Level of evidence GRADE recommendations were used
the Strength of the A modified GRADE (Grading of I: Large, randomized trials to summarize evidence on therapeutic
Evidence Recommendations Assessment, with clear-cut results; low questions.
Development and Evaluation) approach risk of false-positive (alpha)
for assessing the quality of evidence was error or false-negative Level Type of study
used. The quality of the set of included (beta) error of
studies reporting results for an outcome II: Small, randomized trials eviden
was graded as: high, moderate, low or with uncertain results; ce
very low. The interpretation of the moderate to high risk of 1a Systematic review of
grades in these guidelines is: false-positive (alpha) and/or randomized controlled
High: One can be sure that the false-negative (beta) error trials

13
intervention is beneficial, has no effect III: Nonrandomized, 1b Individual randomized
or is harmful. The results, including the contemporaneous controls controlled trial (with
magnitude of the pooled effect, are IV: Nonrandomized, narrow confidence
unlikely to change with new studies. historical controls interval)
Moderate: One can be reasonably sure V: Case series, uncontrolled 1c All cases affected before
that the intervention is beneficial, has no studies, and expert opinion intervention, some or
effect or is harmful. However, the none affected after
magnitude of the pooled effect may Grade of intervention
change with new studies. recommendation 2a Systematic review of
Low: Although it is likely that the A: Supported by at least two cohort studies
intervention is beneficial, has no effect level I investigations 2b Individual cohort study
or is harmful, one cannot be sure. The B: Supported by one level I (including low-quality
magnitude of the pooled effect is investigation randomized controlled
uncertain and is likely to change with C: Supported by level II trial)
new studies. investigations only 2c ‘Outcomes’ research
Very low: One cannot be certain about D: Supported by at least 3a Systematic review of
the effects of the intervention. two level III investigations case-control studies
The criteria used to grade the quality of E: Supported by level IV or 3b Individual case-control
evidence are shown in Table I of the level V evidence study
original guideline document. 4 Case series (and poor-
quality cohort and case-
control studies)

Grade Levels of study

s of
recom
m.
A Consistent level 1
studies
B Consistent level 2 or 3
studies or
extrapolations from
level 1 studies
C Level 4 studies or

14
 extrapolations from
level 2 or 3 studies
D Level 5 evidence or
troublingly inconsistent
or inconclusive studies
of any level
Description of the Data Abstraction and Summary Meta-analyses were used to
Methods Used to Tables of Individual Studies organize information and to
Analyze the Evidence A standardized form was used to extract draw conclusions about
information from relevant studies. overall treatment effect
Systematically extracted data included: from multiple studies on a
study identifiers, setting, design, particular subject. Further
participants, sample size, intervention or details not available.
exposure, control or comparison group,
outcome measures and results. The
following quality characteristics were
recorded for randomized controlled trials
(RCTs): allocation concealment, blinding
of intervention or observers, loss to
follow-up, intention to treat analysis,
analysis adjusted for cluster
randomization (the latter only for
cluster-RCTs). The quality characteristics
recorded for observational studies were
likelihood of reverse causality, selection
bias and measurement bias, loss to
follow-up and analysis adjusted for
confounding.
The studies were stratified according to
the type of intervention or exposure,
study design, birth weight and
gestational age, where possible. Effects
were expressed as relative risks (RR) or
odds ratios (OR) for categorical data,
and as mean differences (MD) or
weighted mean differences (WMD) for

15
continuous data where possible. Where
results adjusted for potential
confounders were available, particularly
for observational studies, they were used
in preference to unadjusted results.
Where results adjusted for potential
confounders were not available,
unadjusted results were used. All studies
reporting on a critical outcome were
summarized in a table of individual
studies (see the Annexes in the original
guideline document).
Pooled Effects
Pooled effects for developing
recommendations were considered,
wherever feasible. If results of three or
more RCTs were available for an
outcome, and the overall quality of
evidence using the Grading of
Recommendations Assessment,
Development and Evaluation (GRADE)
approach was at least "low",
observational studies were not
considered. However, if there were less
than three RCTs for an outcome or the
quality of evidence was "very low", the
effects from RCTs were pooled with
those from available cohort and case-
control studies.
Pooled effects from published systematic
reviews were used if the meta-analysis
was appropriately done, and the reviews
were up to date. However, if any
relevant published study not included in
the systematic review or a
methodological problem with the meta-

16
analysis was identified, the results were
pooled using the "metan" command in
Stata 11.0. For pooling, the author-
reported adjusted effect sizes and
confidence intervals (CIs) were used as
far as possible. Random effects models
for meta-analysis were used if there was
important inconsistency in effects, and
the random effects model was not
unduly affected by small studies. Where
pooling of results was not possible, the
range of effect sizes observed in the
individual studies was used in the
development of recommendations.
Grading the Quality of Evidence
A modified GRADE approach for
assessing the quality of evidence was
used (see the "Rating Scheme for the
Strength of the Evidence" field).
One of the difficulties in using GRADE is
that the evidence base for an outcome
may include studies with varying
methodological quality and sample size.
Therefore, the weight of the studies in
the estimation of the pooled effect was
included to make judgments about the
quality of the set of included studies. The
criteria used to grade the quality of
evidence are shown in Table I in the
original guideline document. The
following briefly describes how these
criteria were used:
Study Design
The included studies were classified as:
1 RCTs –including RCTs or cluster-RCTs
2 Non-randomized experimental studies

17
 3 Observational studies, including cohort
studies and case-control studies
(studies with other observational
designs were not included)
If a majority of evidence was from RCTs,
indicated by over 50% weight in the
pooled effect, a score of 0 was given. A
score of -0.5 was given if a majority of
evidence was from non-randomized
experimental studies, and -1.0 if the
evidence was from observational studies.
See the original guideline document for
the limitations and other details of these
methods.
Methods Used to Expert Consensus Not provided Not provided
Formulate the Other
Recommendations
Description of Formulation of Recommendations Not provided Not provided
Methods Used to The external guideline panel formulated
Formulate the the first version of the recommendations
Recommendations based on the technical review published
in 2006. This version of guidelines was
field tested in health facilities in four
countries - Ghana, India, Pakistan and
Uganda - in 2008-9.
After the evidence base was updated in
2010 and its quality graded using the
modified Grading of Recommendations
Assessment, Development and
Evaluation (GRADE) approach, the World
Health Organization (WHO) staff
prepared the second version of
recommendations in a format consistent
with the new WHO Handbook for
Guideline Development (see the
"Availability of Companion Documents"

18
field).
The Guideline Development Group
(GDG) met once to review the evidence
synthesized in a technical review. The
WHO working group and a consultant
developed the draft guidelines based on
this evidence. This draft was reviewed
electronically by the GDG members and
approved by them.
The GRADE system for grading
recommendations was used. The
strength of a recommendation reflects
the degree of confidence that the
desirable effects of adherence to a
recommendation outweigh the
undesirable effects. The decisions were
made on the basis of evidence of
benefits and harms, quality of evidence,
values and preferences of policy-makers,
health-care providers and parents, and
whether costs are qualitatively justifiable
compared to the benefits in low- and
middle-income countries.

19
 The WHO guidelines were published in year 2011. Because the evidence
behind the recommendations was relatively old, the GDG planned to examine
the recently published systematic review on feeding of LBW infants to update
the evidence and to decide on the need to modify the recommendations.

Step 3: Search and select recommendations

Before searching and selecting the recommendations, the GDG examined the
research questions (RQ) addressed by the WHO and NNF guidelines in the meeting
held in Delhi in late 2015. The group deliberated and enlisted the following steps:

1) Examine the appropriateness and relevance of RQs in WHO feeding guidelines

2) Identify other relevant RQs in NNF Clinical Practice Guidelines to complement
those in WHO guidelines
3) Discuss with other stakeholders – particularly healthcare providers from
secondary level health facilities – to identify research questions that are
relevant to their settings.

Examining WHO LBW feeding guidelines

The WHO guidelines had enlisted 18 priority research questions:

1. In LBW infants (P), what is the effect of feeding mother's own milk (I)
compared with feeding infant formula (C) on critical outcomes - mortality,
severe morbidity, neurodevelopment and anthropometric status (O)?
2. In LBW infants who cannot be fed mother's own milk (P), what is the effect of
feeding donor human milk (I) compared with feeding infant formula (C) on
critical outcomes (O)?
3. In LBW infants who cannot be fed mother's own milk or donor human milk
(P), what is the effect of feeding preterm infant formula (I) compared with
feeding standard infant formula (C) on critical outcomes (O)?
4. In LBW infants who cannot be fed mother's own milk or donor human milk
(P), what is theeffect of feeding nutrient-enriched infant formula from hospital
discharge until 6 months ofage (I) compared with feeding standard infant
formula (C) on critical outcomes (O)?
5. In VLBW infants who are fed mother's own milk or donor human milk (P),
what is the effectof multi-component fortification of breast milk (I) compared
with no fortification of breastmilk (C) on critical outcomes (O)?
6. In VLBW infants who are fed mother's own milk or donor human milk (P),
what is the effectof giving 2-4 Recommended Daily Allowance (RDA) of

20
 vitamin D supplements (I) comparedwith 1 RDA of vitamin D supplements (C)
on critical outcomes (O)?
7. In VLBW infants who are fed mother's own milk or donor human milk (P),
what is the effect of calcium and phosphorus supplementation (I) compared
with no supplementation (C) oncritical outcomes (O)?
8. In VLBW infants who are fed mother's own milk or donor human milk (P),
what is the effectof starting iron supplementation at 2 weeks of age (I)
compared with starting ironsupplementation at 2 months of age (C) on critical
outcomes (O)?
9. In VLBW infants who are fed mother's own milk or donor human milk (P),
what is the effectof daily oral vitamin A supplementation (I) compared with no
supplementation (C) on criticaloutcomes (O)?
10. In LBW infants who are fed mother's own milk or donor human milk (P), what
is the effect ofzinc supplementation (I) compared with no supplementation (C)
on critical outcomes (O)?
11. In LBW infants who are able to breastfeed (P), what is the effect of initiation
of breastfeeding in the first day of life (I) compared with delaying
breastfeeding for more than 24 hours (C) on critical outcomes (O)?
12. In VLBW infants born in settings where total parenteral nutrition is not
possible (P), what is the effect of starting small amounts of oral feeds (about
10 ml/kg per day) in the first few days of life (I) compared with no enteral
feeding (C) on critical outcomes (O)?
13. In LBW infants (P), what is the effect of exclusive breastfeeding for 6 months
(I) compared with an exclusive breastfeeding duration of 4 months or less (C)
on critical outcomes (O)?
14. In LBW infants who need to be fed by an alternative oral feeding method (P),
what is the effect of feeding by a cup or palladai (I) compared with bottle-
feeding (C) on critical outcomes (O)?
15. In VLBW infants who need to be given intragastric tube feeding (P), what is
the effect of bolus intermittent feeding (I) compared with continuous feeding
(C) on critical outcomes (O)?
16. In VLBW infants who need to be given intragastric feeding (P), what is the
effect of orogastric tube feeding (I) compared with nasogastric tube feeding
(C) on critical outcomes (O)?
17. In LBW infants who are fully or mostly fed by an alternative oral feeding
method (P), what is the effect of feeding based on infants’ hunger cues (I)
compared with strict scheduled feeding (C) on critical outcomes (O)?
18. In VLBW infants who need to be fed by an alternative oral feeding method or
given intragastric feeds (P), what is the effect of rapid (>30 ml/kg per day)
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 progression of feeds (I)compared with slow (<20 ml/kg per day) progression
(C) on critical outcomes (O)?

After reviewing the 18 questions, the GDG decided to retain allbut two RQ (question
no. 4 on post-discharge formula and no. 9 on vitamin A supplementation) for the
present guidelines.

Identifying complementary questions from NNF guidelines

The GDG identified eight additional RQs from the NNF practice guidelines. Of these,
the following four were considered to be relevant and important:

1. What should be the frequency of feeds for LBW infants - 2-hourly vs. 3-
hourly?
2. What should be the volume of feeds in LBW infants?
3. What is the role of non-nutritive sucking?
4. How to monitor growth of LBW infants?

Discussion with other stakeholders

The GDG conducted an electronic survey followed by telephonic discussion among

healthcare providers from secondary level facilities to identify additional research
questions. The group did not identify any relevant additional questions.

Recommendations
After enlisting the research questions, the GDG finalized the recommendations by
adopting or adapting the original recommendations from the WHO and NNF
guidelines:

· Adopting a recommendation entails transferring the recommendations

verbatim to the new guideline.
· Adapting a recommendation entails making some changes to the
recommendation. This could be a minor edit in order to ensure local
compatibility with the country setting, or adding precisions to the wording to
clarify the recommendation.

Table 2 enlists all the new recommendations:

22
 Table 2: Final recommendations
New recommendations Adopted/ Recommendations in Reasons for
adapted original guidelines adaptation
What to feed: Choice of milk

1. Low birth weight (LBW) Adopted from Low-birth-weight (LBW) Nil

infants, including those the WHO infants, including those
with very lowbirth weight guidelines with very lowbirth weight
(VLBW), should be fed (VLBW), should be fed
mother’s own milk. mother’s own milk.
2. LBW infants, including Adapted from LBW infants, including The GDG felt it is
those with VLBW, who do the WHO those with VLBW, who not appropriate to
not have access to guidelines cannot be fed mother's use the words ‘who
mother's own milk/ own milk should be fed cannot be fed
whose mother's own milk donor human milk mother’s own milk’.
is insufficient, should be (recommendation relevant The words have
fed donor human milk for settings where safe been modified to
(recommendation relevant and affordable milk- convey the message
for settings where safe and banking facilities are in a more
affordable milk-banking available or can be set appropriate manner.
facilities are available or can up).
be set up).
3. LBW infants, including Adopted from LBW infants, including Nil
those with VLBW, who the WHO those with VLBW, who
cannot be fedmother's guidelines cannot be fed mother's
own milk or donor human own milk or donor human
milk should be fed milk should be fed
standardinfant formula. standard infant formula
(recommendation relevant
VLBW infants who cannot for resource-limited
be fed mother's own milk settings).
or donorhuman milk VLBW infants who cannot
should be given preterm be fed mother's own milk
infant formula if they fail or donor human milk
togain weight despite should be given preterm
adequate feeding with infant formula if they fail
standard infantformula. to gain weight despite
adequate feeding with
standard infant
formula.
4. VLBW infants who are fed Adopted from VLBW infants who are fed Nil
mother’s own milk or the WHO mother’s own milk or
donor human milk should guidelines donor human milk should
not routinely be given not routinely be given
bovine milk-based human bovine milk-based human
milkfortifier. milk
fortifier (recommendation
VLBW infants who fail to relevant for resource-
gain weight despite limited
adequate breastmilk settings).
feeding should be given VLBW infants who fail to
human-milk fortifiers, gain weight despite

23
 preferably those that are adequate breastmilk
human milk based. feeding should be given
human-milk fortifiers,
preferably those that are
human milk based.
What to feed: Supplements
5. LBW infants(1500-2499 Adapted from VLBW infants should be The WHO guidelines
g) should be given the WHO and given vitamin D do not address the
vitamin D supplements at NNF guidelines supplements at a dose issue of vitamin D
a dose of 400 IU per day ranging from400 IU to supplements in LBW
until 6 months of age. 1000 IU per day until 6 infants with BW of
months of age. 1500-2499 g; the
VLBW infants (<1500 g) recommendation is
should be given vitamin D adapted based on
supplements at a dose of the NNF guidelines;
800 IU per day until 6 The ESPGHAN
months of age. guidelines
recommend 800-
1000 IU for preterm
infants; recent
evidence also favors
a higher dose for
preterm VLBW
infants.
6. VLBW infants who are fed Adapted from VLBW infants who are fed The WHO guidelines
mother’s own milk or the WHO mother’s own milk or do not specify the
donor humanmilk should guidelines donor humanmilk should duration of calcium
be given daily calcium be given daily calcium and phosphorus
(120-140 mg/kg per day) (120-140 mg/kg per day) supplements.
andphosphorus (60-90 andphosphorus (60-90
mg/kg per day) mg/kg per day)
supplementation until supplementation during
term gestation (40 thefirst months of life.
weeks’ postmenstrual
age).
7. VLBW infants fed Adapted from VLBW infants fed mother’s The WHO guidelines
mother’s own milk or the WHO and own milk or donor human do not address the
donor human milk should NNF guidelines milk should be given 2-4 issue of iron
be given 2-4 mg/kg per mg/kg per day iron supplements in LBW
day iron supplementation supplementation starting infants with birth
startingat 2 weeks until 6 at 2 weeks until 6 months weights of 1500-
months of age. of age. 2499 g; the
recommendation is
Other LBW infants (1500- adapted based on
2499 g) fed mother’s own the NNF guidelines
milk or donor milk should
be given 2-3 mg/kg per
day iron startingat 6-8
weeks until 6 months of
age.

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8. Routine zinc Adopted from Routine zinc Nil
supplementation for LBW the WHO supplementation for LBW
infants who are guidelines infants who are fed
fedmother's own milk or mother's own milk or
donor human milk is not donor human milk is not
recommended atthe recommended at the
present time, because present time, because
there is not enough there is not enough
evidence ofbenefits to evidence of benefits to
support such a support such a
recommendation. recommendation.
When to initiate feeding?

9. LBW infants (birth weight Adopted from LBW infants who are able Nil
> 1200 g) who are able to the WHO to breastfeed should be
breastfeed should be put guidelines put to the breast as soon
to the breast as soon as as possible after birth
possible after birth when when they are clinically
they are clinicallystable. stable.
10. LBW infants with birth Adapted from VLBW infants should be Recommendation
weight <1200 g should the WHO given 10 ml/kg per day of has been adapted to
be given 10 mL/kg per guidelines enteral feeds,preferably be in sync with NNF
day of enteral feeds, expressed breast milk, guidelines – stable
preferably expressed starting from the first day infants with BW of
breast milk, starting oflife, with the remaining 1200-1499 g can be
from the first day of life, fluid requirement met by initiated on full
with the remaining fluid intravenousfluids enteral feeds from
requirement met by (recommendation relevant day 1 of life.
intravenous fluids. for resource-limited
settings).
How to feed?

11. LBW infants who need Adopted from LBW infants who need to Nil
to be fed by an the WHO be fed by an alternative
alternative oral feeding guidelines oral feedingmethod should
method should be fed by be fed by cup (or palladai,
cup (or palladai, which which is a cup with a
is a cup with abeak) or beak) or spoon.
spoon.
12. VLBW infants requiring Adopted from VLBW infants requiring Nil
intragastric tube feeding the WHO intragastric tube feeding
should be givenbolus guidelines should be given bolus
intermittent feeds. intermittent feeds.

13. In VLBW infants who Adopted from In VLBW infants who need Nil
need to be given the WHO to be given intragastric
intragastric tube guidelines tube feeding,the
feeding, the intragastric intragastric tube may be
tube may be placed placed either by oral or
either by oral or nasal nasal route,depending
route,depending upon upon the preferences of

25
 the preferences of health-care providers.
health-care providers.
14. VLBW infants on Adapted from Frequency of feeding is The NNF guidelines
intragastric tube feeding the NNF decided by the gestational recommend 3 hourly
should be fed 2-hourly. guidelines age, weight and the feeding for infants
clinical condition of the with BW of >1600
Other LBW infants baby (GRADE B). g; for convenience
(1500-2499 g) on and to align with
intragastric tube feeding other
should be fed 3-hourly. recommendations,
the GDG modified it
to weight of 1500 g
15. LBW infants who are Adopted from LBW infants who are fully Nil
fully or mostly fed by an the WHO or mostly fed by an
alternative oral feeding guidelines alternative oral feeding
method should be fed method should be fed
based on infants’ based on infants’ hunger
hunger cues, except cues, except when the
when the infant remains infant remains asleep
asleep beyond 3 hours beyond 3 hours since the
since the last feed last feed
(recommendation (recommendation relevant
relevant to settings with to settings with an
an adequate number of adequate number of
health-care providers) health-care providers)

How much to feed?

16. LBW infants with birth Adapted from The volume of feeds The NNF guidelines
weight >=1200 g should the NNF should be decided taking have suggested 60-
be initiated on 60-80 guidelines into consideration the 80 mL/kg/day in
mL/kg per day of gestational age, infants with BW
enteral feeds, preferably postnatal age and clinical >=1200 g
expressed breast milk, status.
on the first day oflife.
17. In VLBW infants, who Adopted from In VLBW infants who need Nil
need to be fed by an the WHO to be fed by an alternative
alternative oral feeding guidelines oral feeding method or
method or given given intragastric tube
intragastric tube feeds, feeds, feed volumes can
feed volumes can be be increased by up to 30
increased by up to 30 ml/kg per day with careful
ml/kg per day with monitoring for feed
careful monitoring for intolerance
feed intolerance.
18. LBW infants who need Adapted from The volume of feeds The GDG adapted
to be fed by an the NNF should be decided taking the NNF guidelines’
alternative oral feeding guidelines into consideration the recommendation to
method or given gestational age,postnatal make it more clear
intragastric tube feeds, age and clinical status. and avoid ambiguity
should be fed up to 180- The maximum volume of
200 mL/kg per day after feeds may reach up to
26
 1-2 weeks of life. 180-200ml/kg/day
(GRADE D).
Optimal duration of exclusive breastfeeding

19. LBW infants should be Adopted from LBW infants should be Nil
exclusively breastfed the WHO exclusively breastfed until
until 6 months of age. guidelines 6 months of age.
Miscellaneous issues

20. Non-nutritive sucking Adapted from Non-nutritive sucking The NNF guidelines
(NNS) is recommended the NNF accelerates the maturation did not make a clear
in VLBW infants on guidelines of the sucking reflex and recommendation.
intragastric tube feeding has beenobserved to The GDG made a
to improve transition shorten the transition time recommendation
from gavage to breast from gavage to breast after examining the
feeding. feeding. NNS helps in evidence.
initiation andmaintenance,
of successful breast
feeding, during hospital
stay and after discharge.
Growth monitoring

21. LBW infants should be Adapted from All LBW infants should be The GDG adapted
monitored for optimal the NNF checked for weight (daily), the NNF guidelines’
growth by serial weight guidelines head circumference recommendation to
and head circumference (weekly)and length make it simple and
measurement at least (weekly or fort-nightly) easy to use in even
once weekly in the first during their NICU stay. resource restricted
weeks of life, using an Serial growth monitoring settings
appropriate growth allows earlyidentification
chart like Fenton’s of growth faltering.
chart. Fenton’s growth charts
can be used for preterm
babies. WHO Growth
charts (2006) should be
used from corrected age
of 40 weeks into
childhood.

Implementation tools
The GDG has already developed the quick reference guide for wider dissemination.
The guide, along with the standard treatment guidelines, shall be finalized after
incorporating the comments of the external consultation/peer review (timeline: 2
months). Concurrently, the group shall develop patient information document and
quality standards (if applicable) in the next 4-6 months.

27
External consultation/peer review
To be developed

28
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