Feeding of LBW

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Clinical Practice Guidelines - Feeding of Low Birth Weight Neonates
Technical Report · January 2020
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Clinical Practice
Guidelines
Feeding of Low
Birth Weight
Neonates
January 2020
National Neonatology Forum, India

Feeding of Low Birth Weight Neonates
Guideline Development Group (Alphabetical)
Nishanth Banait Ashok Kumar

Sriparna Basu Jogender Kumar
Prakash Desai Arvind Shenoi (Chairperson)
Sourabh Dutta Pradeep Suryawanshi
Reviewers (Alphabetical)
Gopal Agrawal Umesh Vaidya

Sushma Nangia
Editorial Board (Alphabetical)

B D Bhatia Praveen Kumar (Chairperson)
Deepak Chawla Mohit Sahni
Girish Gupta M Jeeva Sankar
Nandkishor S Kabra Sachin Shah
Contents
1. Executive Summary
2. Introduction
3. Scope and Questions for clinical practice
4. Summary of evidence and recommendations
5. References
Annexure 1. GRADE profile tables and search strategies - see online version
Annexure 2. Algorithms and job-aides - see online version
© NNF India Online Version www.nnfi.org/cpg January 2020

Feeding of low birth weight neonates 27
Executive Summary
Low birth weight (LBW) neonates are defined by the WHO as neonates born with a birth weight
of less than 2.5 kg. This heterogenous group consists of neonates born with Extremely Low birth
weight (ELBW) defined as less than 1kg; Very low birth weight neonates (VLBW) defined as
birthweight less than 1.5kg; neonates with varying gestational maturity – term neonates 37-41
weeks with intra-uterine growth retardation, late preterm neonates with gestational ages 34-
36 weeks, preterm neonates 28-33 weeks and extreme preterm neonates less than 28 weeks
gestation. Each of these periods differ in organ maturity, nutrition needs and growth, and every
attempt was made to study these subgroups where feasible. However, evidence is scant in
many areas and subgroups have not been comprehensively studied. This review essentially
summarizes currently available evidence in English literature on LBW feeding.
Nutrition in this critical period is essential for immediate outcomes such as changes in
anthropometry (weight, length and head circumference) as well as adverse effects like
necrotizing enterocolitis (NEC). Nutrition also effects long term adverse outcomes such as
developmental delay, diplegic cerebral palsy, and death during infancy and childhood. This
review has looked for the effects of nutrition in these areas. Further long-term outcomes like risk
of adult onset diseases like myocardial infarction and stroke may also be related to nutrition of
the LBW neonate but have not been included in this review.
The guideline has been developed using standard methods adapted by National
Neonatology Forum in accordance with the process described in the WHO handbook for
guideline development. The detailed methods are described elsewhere in this compilation of
guidelines. Table 1 summarizes the recommendations for practices questions prioritized by the
guideline development group(GDG) in consultation with a wider group of NNF members.
The recommendations made by this group are summarized in Table 1.
NNF India Evidence-based Clinical Practice Guidelines January 2020

Table 1: Summary of recommendations for feeding of low birth weight neonates
S.No. Recommendations Strength of Quality of

recommendations evidence
1. Mother’s own milk is strongly recommended for Strong Not
feeding the low birth weight infant. graded
Specific nutrient supplementation needs to be
made in preterm very low birth weight infants (see
below).
2. (a). If mother’s own milk is not available, Strong, Moderate

pasteurized donor human milk from human milk Conditional
bank, should be used for feeding low birth weight
infants.
Applicable to settings with facilities for providing
donor milk; associated with lower weight gain,
linear growth and head growth and hence need
monitoring and possibly fortification.
(b). If donor human milk is not available, formula
milk is to be considered.
Formula milk will incur a higher cost and may also
be associated with higher risk of necrotizing
enterocolitis and sepsis.
3. Early trophic feeding started within 24 hours of life is Strong, Low

recommended in preterm LBW neonates. Conditional
The recommendation may not be generalized to
extreme preterm or extreme low birth weight
neonates and those with intrauterine growth
restriction for lack of sufficient evidence in this
group of patients.
4. Stable preterm very low birthweight infants may Strong, Moderate

preferably be initiated on progressive enteral Conditional
feeding from the first day of life.
This recommendation may not be generalized to
extreme preterm or extreme low birth weight
neonates and those with intrauterine growth
restriction.
5. Daily feed volumes are to be increased by 30- Strong High

40mL/kg in stable preterm very low birth weight
infants with no signs of feed intolerance.
6. In the absence of other signs of feed intolerance in Weak Low

preterm LBW neonates, neither routine prefeed
abdominal circumference nor prefeed gastric
residue estimation is recommended for assessment
of tolerance to enteral feeds.

7. Preterm infants who cannot feed directly from the Weak Low
breast should be fed by cup, paladai or katori-
spoon, rather than by bottle, to fasten the
transition to direct breast feeding.
8. Preterm very low birth weight infants who do not Weak Very low
accept cup, paladai or katori-spoon feeds should
be fed by either nasogastric or orogastric route of
tube feeding.
9. Intra-gastric route of tube feeding is preferred over Weak Low to

transpyloric route in preterm infants moderate
10. Continuous feeding is not recommended as a Weak Low to

routine strategy for feeding preterm low birth moderate
weight infants receiving intragastric tube feeding.
11. Preterm low birth weight infants with birthweight Weak Low to
>1250 grams and on cup, paladai or katori-spoon very low
feeds or intragastric tube feeding may be given
feeds every three hours.
12. Checking of position of feeding tube (NG/OG) Weak, Conditional Low

after placement and before commencement of
first feed is recommended in LBW infants.
Of the available methods, abdominal x-ray seems
to be the best method for checking the position of
feeding tube.
13. Erythromycin is not to be used routinely for the Weak Very low
management of feed intolerance in preterm LBW
infants.
14. Multi-nutrient fortification of breast milk can be Weak Low to

initiated in preterm LBW infants with birthweight moderate
<1800 g and receiving enteral feeds of at least
50-80 mL/kg/day
For resource limited settings, fortification may be
commenced only for those infants who fail to gain
weight despite adequate breast milk feeding.
15. Routine supplementation of docosahexaenoic Weak Low

acid (DHA) / long chain polyunsaturated fatty acid
(LC-PUFA) is NOT recommended in preterm LBW
infants.
16. Routine oral or intramuscular supplementation of Weak Low

vitamin A is NOT recommended in LBW infants.

17. Oral iron supplements in a daily dose of 2–4 mg/kg Weak Low
of elemental iron is recommended in LBW infants
from 2-4 weeks of life to 12 months of age.
18. Multi-strain probiotics may be initiated in preterm Weak, Conditional Moderate

low birth weight infants from as early as day 1 of life
and continued until 36-37 weeks post-menstrual
age or discharge (whichever is earlier), in neonatal
units with high baseline incidence of necrotizing
enterocolitis.
19. VLBW infants should be given vitamin D Strong Moderate

supplements at a dose ranging from 400 IU to 1000
IU per day from the day of reaching full enteral
feeds to 6 months of age.

Introduction
World Health Organization (WHO) has defined low birth weight (LBW) as neonates who are
born with birth weight of less than 2.5 kg, very low birth weight (VLBW) less than 1.5 kg and
extremely low birth weight (ELBW) less than 1 kg. LBW can be a result of preterm birth (before
37 completed weeks of gestation), small size for gestational age (SGA, defined as weight for
gestation less than 10th percentile), or a combination of both. Overall, 15% to 20% of all births
worldwide are low birth weight, representing more than 20 million births a year with more than
96% in low and middle income (LMIC) countries. [1] Regional estimates of low birth weight
include 28% in south Asia, 13% in sub-Saharan Africa and 9% in Latin America.[2] Every year, 1.1
million babies die from complications of preterm birth and prematurity is the most common
direct cause of neonatal mortality.[3] In India, the main cause of neonatal death in 2015 was
prematurity (43.8%) followed by birth asphyxia and birth trauma (18.9%), and sepsis (13.6%). [4]
LBW infants are at higher risk of fetal and neonatal mortality and morbidity, early growth
restriction, infection, developmental delay, death during infancy and childhood, and an
increased risk of chronic diseases later in life.[5]
By improving the care of LBW infants, global neonatal and infant mortality rates can be
reduced significantly. Optimal nutrition during the neonatal period is essential for growth and
development throughout infancy and into childhood. Experience from both developed and
developing countries has clearly shown that appropriate care of low birth weight (LBW) infants,
with adequate attention to feeding can improve their survival, immediate and longer-term
health and well-being of the individual infant and at population level. [6] Nutritional needs of
infants vary based on gestational age, metabolic state, and physiological complications. This
review focuses on nutrition of relatively well admitted low birth weight neonate without a major
illness.
Scope of the guidelines and target audience
Aim
The primary aim of this guideline is to guide the feeding of low birth weight infants based on
the available evidence by providing recommendations which may be applied in clinical
practice.
Target audience
The primary audience for this guideline includes health-care professionals (neonatologists,
pediatricians, nurses and other practitioners) who are responsible for delivering care for
neonates in different levels of healthcare as well as health program managers and policy-
makers in all settings. The information in this guideline will be useful for developing job aids and
tools for training of health professionals to enhance the delivery of neonatal care.
Population of interest
The guidelines focus on feeding of low birth weight neonates in healthcare settings.
How to use these guidelines

This systematic review on feeding of low birth neonates focusses on the milk, method of
feeding, rapidity of feeding and need for adding specific nutrients. Each recommendation
was graded as strong when there was confidence that the benefits clearly outweigh the
harms, or weak when the benefits probably outweigh the harms, but there was uncertainty
about the trade-offs. A strong or weak recommendation was further classified as situational if
the benefits outweigh the harms in some situations but not in others. For example, some
recommendations were relevant only to settings in low and middle-income countries where
resources are very limited while others were considered relevant only to settings where certain
types of facilities are available. To ensure that each recommendation is correctly understood
and applied in practice, the context of all context-specific recommendations is clearly stated
within each recommendation, and additional remarks are provided where needed. Users of
the guideline should refer to these remarks, which are presented along with the evidence
summaries within the guideline.
Methodology
Nutrition in this critical period is essential for immediate outcomes such as changes in
anthropometry (weight, length and head circumference) as well as adverse effects like
necrotizing enterocolitis (NEC). Nutrition also effects long term adverse outcomes such as
developmental delay, diplegic cerebral palsy, and death during infancy and childhood. This
review has looked for the effects of nutrition in these two areas. Further long-term outcomes
like risk of adult onset diseases like myocardial infarction and stroke may also be related to
nutrition of the LBW neonate but have not been included in this review.
The group decided to focus on five areas of feeding the LBW neonate:
1. What is the best milk for the LBW?
2. What is the best time to initiate feeds, ideal quantity, maximum volume of increment,
and method of detecting feed intolerance.
3. What is the best method of feeding- orogastric, nasogastric, transpyloric, spoon, cup,
paladai, etc.
4. Feeding policy and technique in a sick neonate
5. Nutrition supplements
Post discharge nutrition was not included as part of this review. The group framed 53 questions
and of these 22 questions were shortlisted by a priority poll amongst the members of the GDG
in consultation with a wider group of NNF members. Finally, 20 questions were taken up for a
detailed review.
Questions relevant to clinical practice
1. Should Mother’s own milk vs. Formula milk/Donor human milk be used for feeding
preterm or low birth weight infants?
2. What is the best choice of milk for feeding when Mother’s milk is not available?
3. What is the role of trophic feeding?

4. What is the optimum time for initiation of progressive enteral feeding in very low birth
weight infants? (early vs. late)
5. What is the optimum time to achieve full volume feeding in LBW infants? (slow vs. rapid
advancement of feeding)
6. Is there any role of monitoring prefeed abdominal circumference and/or gastric
aspiration before giving the feed?
7. If direct breastfeeding is not possible then what is the best mode of enteral feeding?
(tube feeding/ cup feeding/ paladai/ spoon/ syringe)
8. What is the best route of tube feeding in VLBW/LBW infants (orogastric vs.
nasogastric)?
9. What is the best route of tube feeding in VLBW/LBW infants (transpyloric vs.
intragastric)?
10. What is the best schedule of feeding in VLBW infants (continuous vs. bolus)?
11. What is the best schedule of feeding in VLBW infants (2 hourly vs. 3 hourly)?
12. Should we check the position of NG/OG tube before each feeding and how?
13. Is there any role of prokinetics in feeding intolerance?
14. What is the role of human milk fortifier in LBW neonates?
15. Is there a role of supplementing DHA in LBW neonates?
16. Do we need to give Vitamin A supplementation to LBW neonates?
17. Is there role of Iron supplementation in LBW neonates?
18. Is there any role of Probiotics in LBW neonates?
19. Is there role of Vitamin D supplementation in LBW infants?
Outcomes of interest
For each question, the following outcomes were considered critical

1. Mortality
2. Necrotizing enterocolitis
The following outcomes were considered to be important

1. Growth and anthropometry
2. Neuro-developmental disability
3. Duration of hospital stay
Benefits and harms in critical outcomes formed the basis of the recommendations for each
question.
A systematic review of literature was done and a standardized form was used to extract
relevant information from studies. Systematically extracted data included: study identifiers,
setting, design, participants, sample size, intervention or exposure, control or comparison
group, outcome measures and results. The following quality characteristics were recorded for
all studies: allocation concealment or risk of selection bias (observational studies), blinding of
intervention or observers or risk of measurement bias, loss to follow up, intention to treat analysis
or adjustment for confounding factors, and analysis adjusted for cluster randomization (the
latter only for cluster-randomized controlled trials, RCTs).

Interpretation of strong and conditional recommendations
We used GRADE approach for assessing the quality of evidence and the recommendations.
The quality of the set of included studies reporting results for an outcome was graded as: high,
moderate, low or very low. 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 relative to benefits in low- and middle-
income countries.
Evidence Review and Formulation of recommendations
Methodology
Using the assembled list of priority questions and critical outcomes from the scoping exercise,
the guideline development group, along with reviewers identified systematic reviews that
were either relevant or potentially relevant and assessed whether they needed to be updated.
A systematic review was considered to be out of date if the last search date was two years or
more prior to the date of assessment. If any relevant review was found to be out of date, it was
updated.
Search strategy
Cochrane systematic reviews were the primary source of evidence for the recommendations
included in this guideline. In addition, key databases searched included the Cochrane
database of systematic reviews of RCTs, the Cochrane controlled trials register and MEDLINE
(1966 to August 2019). The reference lists of relevant articles and a number of key journals were
hand searched. Details of search strategy are provided in the online annexure.
Data abstraction and summary tablsof individual studies
A standardized form was used to extract information from relevant studies. Systematically
extracted data included: study identifiers, setting, design, participants, sample size,
intervention or exposure, control or comparison group, outcome measures and results. The
following quality characteristics were recorded for 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
continuous data where possible. All studies reporting on a critical outcome were summarized
in a table of individual studies.

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 GRADE approach was at least "low", observational studies were not considered.
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-analysis was
identified, the results were pooled in RevMan 5. 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 an 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.
Quality assessment
Quality assessment of the body of evidence for each outcome was performed using the
Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
The GRADE approach was used for all the critical outcomes identified in the PICOs, and a
GRADE profile was prepared for each quantitative outcome within each PICO. Accordingly,
the quality of evidence for each outcome was rated as “high,'' “moderate,” “low,” or “very
low” based on a set of criteria. As a baseline, RCTs provided “high-quality” evidence, while
non-randomized trials and observational studies provided “low-quality” evidence. This
baseline quality rating was then downgraded based on consideration of risk of bias,
inconsistency, imprecision, indirectness and publication bias. For observational studies, other
considerations, such as magnitude of effect, could lead to upgrading of the rating if there
were no limitations that indicated a need for downgrading.
Risk of bias
Inconsistency of the results: The similarity in the results for a given outcome was assessed by
exploring the magnitude of differences in the direction and size of effects observed from
different studies. The quality of evidence was not downgraded when the directions of the
findings were similar and confidence limits overlapped, whereas quality was downgraded
when the results were in different directions and confidence limits showed minimal overlap.
Indirectness: Rating of the quality of evidence were downgraded where there were serious or
very serious concerns regarding the directness of the evidence, i.e. where there were
important differences between the research reported and the context for which the
recommendations are being prepared. Such differences were related, for instance, to
populations, interventions, comparisons or outcomes.
Imprecision: The degree of uncertainty around the estimate of effect was assessed. As this was
often a function of sample size and number of events, studies with relatively few participants
or events (and thus wide confidence intervals around effect estimates) were downgraded for
imprecision.

Publication bias: Quality rating could also be affected by perceived or statistical evidence of
bias that may have led to underestimation or overestimation of the effect of an intervention
as a result of selective publication based on study results. Where publication bias was strongly
suspected, evidence was downgraded by one level.
GRADE profile software was used to construct “Summary of Findings” tables for each priority
question; these tables include the assessments and judgements relating to the elements
described above and the illustrative comparative risks for each outcome. Relevant
information and data were extracted in a consistent manner from the systematic reviews
relating to each priority question by applying the following procedures. First, up-to-date review
documents and/or data (e.g. RevMan file) were obtained from the Cochrane Library.
Secondly, analyses relevant to the critical outcomes were identified and selected. The data
were then imported from the RevMan file (for Cochrane reviews) or manually entered into the
GRADE profilers (for non-Cochane reviews). For each outcome, GRADE assessment criteria (as
described above) were applied to evaluate the quality of the evidence. In the final step of
the assessment process, GRADE evidence profiles were generated for each priority question.
Document review
The GDG personally met on two occasions and prepared a draft of the full guideline
document with revisions to accurately reflect the deliberations and decisions of the GDG
participants. This draft guideline was then sent electronically to the GDG participants for further
comments. The inputs of the peer reviewers were included in the guideline document and
further revisions were made to the guideline draft as needed. After the peer review process,
the revised version was prepared.

Questions, Evidence summaries and Recommendations
Practice Question 1 : Should Mother’s own milk vs. Formula milk/Donor human milk be used for
feeding preterm or low birth weight infants?[7–13]
Table 2: Summary of previous guidelines
Association / Professional Recommendation Remarks

body
WHO Optimal feeding of Breast feeding or mother’s Extensive review of data.
Low birth weight infants own expressed milk is the
Technical review 2006[11] best option.
ESPGHAN 2010[8] Recommended human milk Focused on nutrient
with need for added requirement of preterm
nutrients neonates
NNF feeding guideline Breast feeding or mother’s Consensus guidelines no
2011[6] own milk grading of evidence
WHO Optimal feeding of LBW infants should be fed Strong recommendation
LBW in low and middle Mother’s own milk based on moderate quality
income countries 2011[7] of evidence.
The WHO recommendations[7] on optimal feeding of low birth weight infants had reviewed all
the cohort studies till then and concluded that there is strong evidence to recommend
mother’s own milk. Following this no further trials were found that have addressed this issue and
it is unlikely that any further trials will be conducted as the evidence is overwhelming.
Maternal breast milk remains the default choice of enteral nutrition for the LBW neonate.
Observational studies, and meta-analyses of trials comparing cohorts of neonates fed with
formula versus breast milk, suggest that feeding with breast milk has the following benefits and
need supplementation as below.
1. There was no study which examined the impact of mother’s own milk feeding
on mortality.
2. Mother’s own milk has been associated with reduced risk of infection RR 0.44 –
0.56 (0.24, 0.82)[7]
3. Mother’s own milk feeding is associated with increased cognitive
development scores adjusted mean difference about 5, including in SGA term
infants.[7]
4. Mother’s own milk feeding is reported with slower growth in length and weight
compared to formula fed neonates but this difference has not been found
significant at 18 months follow up.[7]
5. LBW Neonates fed exclusively on un-supplemented mother’s own milk have
been reported in case series to develop iron deficiency, osteopenia, zinc
deficiency vitamin A and vitamin D deficiency. Hence ESPGHAN [8] has
recommended appropriate supplementation of these nutrients particularly in
the Very low birth weight neonates.
Based on the existing data WHO, UNICEF and European Society of Pediatric Gastroenterology
and Nutrition (ESPGHAN) strongly recommend that use of Mother’s Own Milk for the Low birth
weight infant. It is unlikely that any further trials will be conducted to confirm or refute this

conclusion. This recommendation strongly endorses the use of Mother’s own milk for the low
birth weight infant.
RECOMMENDATION 1
Mother's own milk (MOM) is strongly recommended for feeding the low birth weight infant.
Specific nutrient supplementation needs to be made in preterm very low birth weight
infants.
Strong recommendation, not graded
Practice Question 2 : If Mother’s own milk is NOT available should formula milk vs. donor milk
be used for feeding preterm or low birth weight infants? [7–9,14]
Summary of Evidence
The outcomes assessed in this meta-analysis were growth, necrotizing enterocolitis, all-cause
mortality and neurodevelopmental disability. Presently available evidence of 11 trials (1809
infants) fulfilling the inclusion criteria showed that formula-fed infants had higher in-hospital
rates of weight gain, linear growth and head growth (moderate quality evidence).
However, formula feeding was associated with a significantly increased risk of necrotizing
enterocolitis (moderate quality evidence). There was no evidence of an effect on long-term
growth or neurodevelopment with either of the interventions. Considering the low socio-
economic status and poor hygienic condition of our country, there should be a word of
caution for the use of formula milk, as incidence of sepsis is already very high in majority of the
neonatal care units of India. Another prohibitive factor is the high cost associated with formula
feeding, which often leads to a tendency of over-dilution and poor nutrition.
Only pasteurized donor human milk from human milk bank is recommended for feeding.
Moreover, it needs adequate fortification for feeding preterm low birth weight infants.
RECOMMENDATION 2
(a). If mother’s own milk is not available, pasteurized donor human milk from human milk
bank, should be used for feeding low birth weight infants.
Applicable to settings with facilities for providing donor milk; associated with lower weight
gain, linear growth and head growth and hence need monitoring and possibly fortification.
(b). If donor human milk is not available, formula milk is to be considered.
Formula milk is costly and may also be associated with higher risk of necrotizing enterocolitis
and sepsis. Utmost care should be taken for maintenance of asepsis and proper dilution.
Strong Conditional recommendation, based on Moderate quality evidence

Practice Question 3 : Should trophic feeding vs. enteral fasting be used for very preterm or very
low birth weight infants ?[15]
Summary of Evidence
In a metanalysis of nine randomized controlled trials, 754 infants were included. The
metanalysis looked at the effect of early trophic feeding versus enteral fasting on feed
tolerance, growth and development, and the incidence of NEC and invasive infection and
mortality in very preterm or VLBW infants. The metanalysis showed that there is no difference
in days to reach full feeds ( feed intolerance) (MD) -1.05 (95% (CI) -2.61 to 0.51) days. The
evidence was downgraded to low because of risk of bias and significant inconsistency.
Similarly low quality evidence suggests, no significant difference for NEC (RR) 1.07 (95% CI 0.67
to 1.70). The quality of evidence was downgraded to low because of risk of bias and
imprecision (wide CI). The other outcomes like mortality, short term growth, invasive infections
and duration of hospital stay also did not show significant difference between the early trophic
versus fasting group. The quality of the evidence for these outcomes was downgraded to low
because of serious risk of bias, imprecision and inconsistency.
When trophic feeds are started within the first 96 hours and continued for at least one week, it
did not increase the feeding tolerance and did not increase the risk of NEC. Early trophic feeds
is preferred to increase gastrointestinal maturation, to reduce cholestasis and phototherapy
requirement. Early introduction of trophic feeds compared to fasting had a trend towards
reaching full feeds earlier but in a non-significant way (MD)− 1.05 days (95% CI −2.61, 0.51).
RECOMMENDATION 3
Early trophic feeding started within 24 hours of life is recommended in preterm LBW
neonates.
The recommendation may not be generalized to extreme preterm or extreme low birth
weight neonates and those with intrauterine growth restriction for lack of sufficient evidence
in this group of patients.
Strong Conditional recommendation, Low quality evidence

Practice Question 4: Should delayed vs. early introduction of progressive enteral feeding be
used for very low birth weight infants?[16]
Summary of Evidence
Analyses of data from nine randomized controlled trials with 1106 infants did not provide
evidence that delayed introduction of progressive enteral feeds reduced the risk of NEC.
Meta-analysis of data from these trials did not indicate an effect on all- cause mortality (RR)
1.18, 95% (CI) 0.75 to 1.88. Meta-analysis did not detect a statistically significant effect for NEC
(RR) 0.93, 95% (CI) 0.64 to 1.34. The quality of this evidence was downgraded to moderate for
significant risk of bias.
The median time to establish full enteral feeding was longer in the delayed introduction group
but the reports did not provide data to allow quantitative synthesis. For other outcomes
moderate evidence suggested no difference in invasive infections, feed intolerance and
growth between early and delayed introduction of enteral feeding. The duration of hospital
stay was also not different between the groups, but the quality of evidence of this is low
because of risk of bias and significant inconsistency.
Four trials recruited only infants with intrauterine growth restriction and abnormal flow velocities
detected on antenatal Doppler studies. Meta-analysis did not detect any statistically
significant differences in the incidence of NEC or mortality. The quality of evidence was
downgraded to moderate for risk of bias.
RECOMMENDATION 4
Stable preterm very low birthweight infants may preferably be initiated on progressive
enteral feeding from the first day of life.
This recommendation may not be generalized to extreme preterm or extreme low birth
weight neonates and those with intrauterine growth restriction.
Strong Conditional recommendation, Moderate quality evidence

Practice Question 5: Should slow vs. faster rates of feed advancement be used for very low
birthweight infants?[17,18]
Summary of Evidence
A meta-analysis of 10 RCTs in which a total of 3753 infants participated (2804 infants

participated in one large trial). Most participants were stable very preterm infants of birth
weight appropriate for gestation. About one-third of all participants were ELBW, and about
one-fifth were small for gestational age (SGA), growth-restricted, or compromised in utero, as
indicated by absent or reversed end-diastolic flow velocity (AREDFV) in the fetal umbilical
artery. Trials typically defined slow advancement as daily increments of 15 to 20 mL/kg, and
faster advancement as daily increments of 30 to 40 mL/kg.
Meta-analyses did not show effects on risk of NEC (RR) 1.07, 95% (CI) 0.83 to 1.39; or all-cause
mortality (RR) 1.15, 95% (CI )0.93 to 1.42. Subgroup analyses of extremely preterm or ELBW
infants, or of SGA or growth-restricted or growth-compromised infants, showed no evidence of
an effect on risk of NEC or death.
Slow feed advancement delayed establishment of full enteral nutrition by between about one
and five days. Meta-analysis showed borderline increased risk of invasive infection (RR) 1.15,
95% (CI) 1.00 to 1.32. The quality of evidence for these primary outcomes were moderate,
downgraded from high because of lack of blinding in the included trials. The included trials
did not show consistent evidence of an important effect on duration of hospital admission and
the reports did not provide data to allow quantitative synthesis.
We could not include a very recent publication from October 2019 as the search was restricted
to August 2019 and practical constraints. But the outcomes of this study compliments the
above findings.[18] The SIFT trial[18] study showed that there was no significant difference in
survival without moderate or severe neurodevelopmental disability at 24 months in very
preterm or very-low-birth-weight infants with a strategy of advancing milk feeding volumes in
daily increments of 30 ml per kilogram as compared with 18 mL per kilogram.
RECOMMENDATION 5
Daily feed volumes are to be increased by 30-40 mL/kg in stable preterm very low birth
weight infants with no signs of feed intolerance.
Current evidence suggests that this recommendation is also applicable to subgroups of

neonates with IUGR, extremely low birth weight, and those with absent or reversed end
diastolic flow .
Strong recommendation, High quality evidence

Practice Question 6a.: Should pre feed abdominal circumference measurement vs. no
abdominal circumference be used for VLBW infants?[19]
Summary of Evidence
There are no randomized controlled trials ascertaining the role of abdominal circumference
(AC) measurement as a sole parameter, in feeding outcomes and NEC.
In a single prospective study with 50 participants the abdominal distension (labelled as

abdominal circumference >1.5 cm) did not have predictive value for time to reach full feeds.
The mean number of days with abdominal distention prior to full gavage feedings being
achieved was 0.03 +/- 0.07 (range 0.00– 0.30). The quality of evidence is graded as low as it is
a single prospective study.
We considered two randomized controlled trials comparing AC with Gastric residual volume
(GRV). In both the studies NEC has not been reported as primary outcome, and time to reach
full feeds has been reported in comparison ( AC vs GRV) and not as AC vs no AC or GRV vs
no GRV. This was a limitation in considering these studies for the purpose of answering this
question and grading evidence. In addition, the current available evidence is suggesting
minimal role for GRV as predictor for feeding intolerance and NEC.
Evidence also suggests that there is significant inter and intra-observer variability in measuring
AC and that there can be up to 3.5 cm variation in AC during a feeding cycle in preterm
babies.
Practice Question 6b.: Should routine pre-feed gastric residual volume testing vs no routine
gastric residual volume testing be done to assess feed intolerance in low birth weight and very
low birthweight infant?[20–23]
Summary of Evidence
We identified three RCT’s (620 neonates) which compared routine gastric residual volume
(GRV) testing versus no routine GRV testing in low and very low birth weight neonates. Sepsis
and NEC were considered as critical outcomes. The meta-analysis of the 3 trials has shown that
there is no effect of selective gastric residue aspiration on incidence of sepsis, NEC>= stage 2,
and length of hospital stay. The quality of evidence was graded as low due to imprecision and
serious risk of bias. The other important outcomes were time to reach full feeds, length of
hospital stay and any stage NEC. There is low-quality evidence from 3 RCT’s (downgraded due
to risk of bias in assessing NEC and imprecision as the risk difference is almost negligible) that
routine pre-feed gastric residue estimation leads to increased risk of NEC. This finding was
consistent in all three trials. Also, all three trials consistently reported that routine gastric residual
testing delays the time to reach full feeds (downgraded as low-quality evidence due to risk of
bias and lack of meaningful clinical precision). There was no difference in the length of the
hospital stay (judged as very low quality due to imprecision, risk of bias, and inconsistency).
Since, the event rate for the critical outcomes (sepsis and NEC>/= stage 2) is very low (< 5%)
and the risk estimates for these outcomes are imprecise. So, for these outcomes, the overall
certainty is low.

There is low-quality evidence that routine pre-feed gastric residue estimation leads to
increased risk of NEC (any stage) and delays the time to reach full feeds (120 ml/kg/day).
Therefore, the evidence is against the practice of routine pre feed GRV aspiration.
There are no costs associated with abandoning the practice of routine prefeed GRV testing in
LBW neonates which do not have any other signs of feed intolerance.
RECOMMENDATION 6
In the absence of other signs of feed intolerance in preterm LBW neonates, neither routine
prefeed abdominal circumference nor prefeed gastric residue estimation is recommended
for assessment of tolerance to enteral feeds.
Weak recommendation, based on Low quality evidence
Practice Question 7: Should cup feeding vs. other modes of supplemental enteral feeding
(bottle/tube feeding) be used in preterm infants unable to fully breast feed? [24–34]
Summary of Evidence
The critical outcomes considered were rates of mortality, sepsis, breastfeeding rates at
discharge, and weight gain during the hospital stay. From the existing literature, there is no
information on the comparison of the mortality rate or sepsis rate among the various methods.
Four randomized controlled trials (957 infants) assessed any breastfeeding (not exclusive) at
discharge. The meta-analysis of these 4 trials showed that the breastfeeding rates at the time
of hospital discharge are better with the cup-feeding as compared to other supplemental
modes of feeding. The evidence was downgraded to low-quality due to serious risk of bias and
inconsistency of the definitions used and the results among the studies.
Only one trial assessed the daily weight gain and found that there was no difference in weight
gain (very low-quality evidence). Only one study assessed the gestational age at discharge
and found that there was no difference in the gestational age at discharge (very low-quality
evidence). Two studies assessed average time per feed and did not find any difference (meta-
analysis was not done due to significant heterogeneity). Two studies assessed the length of
hospital stay and found considerable variation in results and in the direction of effect (meta-
analysis was not done due to significant heterogeneity). Only one trial reported desaturations
during feeding and didn't find any difference (very high risk of bias and selective reporting).
So overall, there is very low-quality evidence to suggest that breastfeeding rates at discharge
and on follow-up are better with cup feeding as compared to bottle or other supplemental
modes of feeding. No trials were found which compared the use of palladai / spoon feeds
versus cup or bottle feeds. The group however feels that there is a high probability that katori-
spoon and paladai feeding resembles cup feeding strongly enough to universalize this
recommendation to both these indigenous methods till further studies are available.
There are concerns about bacterial contamination of milk in bottles, therefore WHO and
UNICEF recommend cup feeding in low-resource settings.

RECOMMENDATION 7
Preterm infants who cannot feed directly from the breast should be fed by cup, paladai or
katori-spoon, rather than by bottle, to fasten the transition to direct breast feeding.
Practice Question 8: Should nasogastric vs. orogastric tube feeding be used in feeding LBW
infants[35–44]
Summary of Evidence
Very few studies have tried to look into superiority of either nasogastric or orogastric feeding
tube placement for enteral feeding in preterm or low birth weight infants in relation to feeding
tolerance, growth and development, and adverse events.
Critical outcomes considered in this meta-analysis were time to establish full enteral tube
feeds, time to regain birth weight and need for oxygen supplementation. Only a single
randomized controlled trial (RCT) of small sample size (n = 46) and poor methodological quality
assessed these outcomes. No significant difference in any of the outcomes was found.
Another two poor quality RCTs assessed the incidences of apnea, bradycardia and
desaturation episodes in association with nasogastric versus orogastric placement of feeding
tubes. Though there was no immediate difference, one RCT documented significantly more
recorded episodes of apnea in nasogastric tube group on the seventh day. Because of
significant heterogeneity (wide variability of study design and definitions used for apnea),
meta-analysis of the outcomes could not be undertaken.
So, overall, very low-quality evidence does not establish superiority of any mode of feeding
tube placement (nasogastric vs. orogastric) in preterm low birth weight infants. However, there
are concerns of apnea, bradycardia and desaturation episodes in relation to prolonged (7
days and more) nasogastric tube feeding.
RECOMMENDATION 8
Preterm very low birth weight infants who do not accept cup, paladai or katori-spoon feeds
should be fed by either nasogastric or orogastric route of tube feeding.
Weak recommendation, based on Very low quality evidence

Practice Question 9 : Should transpyloric route vs. Gastric route be used for tube feeding in
preterm infants?[45–52]
Summary of Evidence
Outcomes considered for this meta-analysis were growth (weight, length and head-
circumference gain velocity), death prior hospital discharge, adverse events such as
gastrointestinal disturbances including diarrhea, necrotizing enterocolitis and aspiration
pneumonia.
Four RCTs (n = 93) of low methodological quality documented significantly higher weight and
length gain velocity in association with transpyloric feeding in preterm infants. Two RCTs (n
= 75) of low methodological quality did not find any difference in head-circumference gain
velocity with either of the two methods. Similarly, five RCTs (n = 165) of low methodological
quality did not find any difference in mortality during hospital stay with either intervention.
Six RCTs (n = 219) of moderate methodological quality documented significantly higher

incidences of gastrointestinal disturbances including diarrhea in association with transpyloric
feeding, though the incidences of necrotizing enterocolitis (7 RCTS, n = 198, moderate-quality
evidence) and aspiration pneumonia (6 RCTs, n = 171, low- quality evidence) were similar with
both the interventions.
However, insertion and maintenance of transpyloric tube placement requires considerable

expertise, which is not available in Level II nursery set-ups of India. Therefore, though
transpyloric tube feeding is associated with better weight and length gain velocity, it is
associated with higher incidences of gastrointestinal disturbances including diarrhea (low to
moderate-quality evidence), and requires considerable expertise.
RECOMMENDATION 9
Intra-gastric route of tube feeding is preferred over transpyloric route in preterm infants .
Weak recommendation, based on low to moderate quality of evidence
Practice Question 10: Should continuous intragastric tube feeding vs. intermittent bolus tube
feeding be used for preterm low birthweight infants?[53–65]
Summary of Evidence
Major outcomes analyzed in this meta-analysis are days to reach full feeds, full enteral feeding
achieved in 28 days, days to regain birth weight, growth (weight, length, head circumference,
triceps skin fold thickness gain velocity), duration of mechanical ventilation, necrotizing
enterocolitis, apneic episodes, sepsis and death.

Five RCTs (n = 424) did not find any significant difference between continuous intragastric tube
feeding and intermittent bolus tube feeding in preterm low birth weight infants in days to reach
full feeds (moderate quality evidence). One (n = 246) and five (6 = 647) RCT(s) did not find any
difference between the interventions with respect to full enteral feeding achieved in 28 days
and days to regain birth weight, respectively (both moderate quality evidence).
Moderate quality evidence showed that there was no difference in improvement in growth
parameters (per day or per week weight gain, length gain, head circumference gain and
change in triceps skinfold thickness), duration of mechanical ventilation (two RCTs, n = 326)
and complications including NEC (Bell's Stage II and beyond) (five RCTs, n = 516), number of
apneic episodes/day (two RCTs, n = 307), sepsis (one RCT, n = 246) and mortality (one RCT, n
= 246) between continuous and intermittent bolus feeding.
One study reported significantly lower mean daily gastric residual volumes and number of
patients with feeding interruptions in association with intermittent bolus feeding compared to
continuous feeding (low quality evidence).
Continuous bolus feeding requires the facility for syringe pump, involves large cost and
continuous supervision. Therefore, it may not be feasible in Level II neonatal care set ups.
RECOMMENDATION 10
Continuous feeding is not recommended as a routine strategy for feeding preterm low birth
weight infants receiving intragastric tube feeding.
Weak recommendation, based on low to moderate quality evidence
Practice Question 11: Should three hourly feeding vs Two hourly feeding be used for stable very
low birthweight infants?[66–70]
Summary of Evidence
The metanalysis of the four trials has shown that there is no difference in any stage NEC, feed
intolerance, hypoglycemia, and time to reach full enteral feeds among two groups (low-
quality evidence, downgraded for serious risk of bias and imprecision). The meta-analyses of
three trials (including 350 neonates) have shown that the three hourly feeding groups help in
regaining birth weight faster as compared to 2 hourly feeding schedules (low-quality
evidence, downgraded due to serious risk of bias and inconsistency among the reported
results in the individual trials. One trial (92 neonates) from India has shown that three hourly
feeding schedules can reduce the total time spent in feeding by the nurses by 22 minutes (very
low-quality evidence). So, the overall effects seem to be trivial benefit by three hourly feeding
schedules.
The event rate for the critical outcome (NEC) is low (7.3 and 7.8%) and the risk estimates for
these outcomes are imprecise. Also, the sample size is small (n-411). Therefore, the overall

certainty of the evidence for critical outcomes like NEC will be very low. Similarly, for adverse
effects like feed intolerance and hypoglycemia, the certainty will be very low (small sample,
imprecise results, and risk of bias). For favorable outcomes like time to reach full feeds and
nursing time spent the certainty will be low to very low. Therefore, the overall certainty was
judged as very low.
As the ELBW population in trials was very less and subgroup analysis was not done, these results
cannot be applied to those infants. One study has shown that the extremely low-birth-weight
infants reach full enteral feeds earlier when fed 2-hourly compared with 3-hourly. Therefore,
we suggest to continue 2 hourly feeding schedules in ELBW population.
RECOMMENDATION 11
Preterm low birth weight infants with birthweight >1250 grams and on cup, paladai or katori-
spoon feeds or intragastric tube feeding may be given feeds fed every three hours.
Weak recommendation, based on low to very-low quality evidence
Practice Question 12: Should checking of position of feeding tube vs. no checking of position
of feeding tube be used for preterm infants before feeding? [71–92]
Summary of Evidence
Though confirmation of the position of feeding tube before enteral feeding or any other
procedure in preterm infants have been advocated by many studies, there is paucity of good
quality evidence for the method of checking the same. Various observational studies have
assessed a variety of different methods for verifying placement of enteral feeding tubes in
newborns including gastric secretion aspiration, epigastric region auscultation, checking
aspirated secretion’s pH, pepsin, trypsin and bilirubin, secretion color, presence of CO2 test,
acid test with litmus paper, ultrasonography, reading diaphragm’s electrical activity,
electromagnetic tracing and the use of indigo carmine at 0.01%.
Since there was no RCT or good quality case-control study, meta-analysis of evidence was not
possible.
Though abdominal radiographs are considered “gold standard” for verifying placement of
feeding tubes, but the risks of radiation exposure, availability of portable x-ray machine and
handling of infants often limit the use of radiographs in neonatal age group. pH analysis of fluid
aspirated from feeding tubes to verify the placement in stomach has been evaluated in
several studies and found to be an easy and effective methods. Though checking the mark
of the feeding tube, aspiration to check the contents and injection of air and listening to the
sound over stomach are widely practiced across the neonatal care units, these practices are
not supported by evidence.

Existing International guidelines recommend the use of pH test indicators as the method of
choice to correctly verify the position of naso/orogastric tubes. A minimum of 0.5 – 1 mL of
gastric content should be aspirated and a reading between 0-5.5 in pH indicator strips is
confirmatory for the intra-gastric position of the feeding tube.
RECOMMENDATION 12
Checking of position of feeding tube (NG/OG) after placement and before

commencement of first feed is recommended in LBW infants.
Of the available methods, abdominal x-ray seems to be the best method for checking the
position of feeding tube.
Practice Question 13: Should Erythromycin vs. placebo/ no erythromycin be used for feed
intolerance in preterm infants as a rescue therapy?[93–102]
Summary of Evidence
We included randomized trials where erythromycin was used as rescue therapy only. The trials
with prophylactic erythromycin were not included in the review. We divided the population
into < 32 weeks and >/= 32 weeks preterm infants and low dose (< 12 mg/kg/day) vs high dose
(> 12 mg/kg/day) erythromycin. This division is important as per the physiology and MOA of
erythromycin. As the mechanism of the low and high dose is different, it will be inappropriate
to combine the studies of low dose and high dose. Our critical outcomes were sepsis, NEC,
and death.
Less than 32 weeks gestation
There were 6 RCTs for high dose and 2 for low dose. Of them only 4 from high dose and one
from low dose trials reported our critical outcomes. The low dose does not have any impact
on sepsis, NEC, or death (moderate-quality evidence, downgraded due to imprecision). The
high dose also does not have any impact on sepsis, NEC (low-quality evidence, downgraded
due to serious risk of bias and imprecision). There is moderate-quality evidence that high dose
erythromycin does not have any impact on the mortality rate (moderate-quality evidence,
downgraded due to imprecision).
There is very low-quality evidence (downgraded due to serious risk of bias and extreme
heterogeneity of 76%) that high dose erythromycin in infants less than 32 weeks, helps in

reaching full enteral feeds earlier by 6.82 days (95 % CI 5.37- 8.28). For any other positive
outcome, there was no advantage of erythromycin over placebo.
There is concern about the TPN related cholestasis secondary to prolonged use of TPN in infants
with frequent feed intolerance. There is low-quality evidence (downgraded due to very serious
risk of bias due to variation in the definition of cholestasis and lack of blinding for assessing
outcome in some trials) that the use of high dose erythromycin in less than 32 weeks infants
leads to 50% reduction in the risk of cholestasis. There are concerns about the emergence of
antibiotic resistance against erythromycin. Although there was no difference in the sepsis rates
among the two groups, this aspect has not been addressed well in the trials.
More than / equal to 32 weeks gestation
There are three studies of which 2 used high dose and one used low dose (subgroup analysis).
There was no difference between sepsis, NEC, and mortality rates among the erythromycin
versus the placebo group (low to moderate quality).
In summary, there is very low-quality evidence that high dose erythromycin (> 12 mg/kg/day)
in infants less than 32 weeks, helps in reaching full enteral feeds earlier by 6.82 days (95 % CI
5.37- 8.28). There is no impact on any other outcome.
RECOMMENDATION 13
Erythromycin is not to be used routinely for the management of feed intolerance in preterm
LBW infants.
Weak recommendation, based on very-low quality evidence

Practice Question 14: Should Human milk fortification vs. No fortification be used for
supplementing feeding in LBW infants?[103–112]
Association / Professional Recommendation Remarks

body
WHO Optimal feeding of VLBW infants who are fed mother’s Weak situational
LBW in low and middle own milk or donor human recommendation
income countries 2011[7] milk should not routinely be given relevant to resource-
bovine milk-based human milk limited settings, based on
fortifier (recommendation relevant low to very low
for resource-limited quality evidence for no
settings). benefits in critical
VLBW infants who fail to gain outcomes and higher
weight despite adequate costs)
breastmilk feeding should be
given human-milk fortifiers,
preferably
those that are human milk based.
Commentary from The Committee advocates the use Recommended Energy
ESPGHAN 2010[8] of human milk for preterm intake 110–135
infants as standard practice, kcal/kg/day and Protein
provided it is fortified with added 3.5–4.5 g/kg/day
nutrients where necessary to meet
requirements.
European Milk Bank Recommends fortification of HM Individualized fortification
Association (EMBA) for preterm infants with BW<1800g ( Targeted or Adjusted )
Working Group(WG) on when volume reaches 50-80 is desirable.
HM Fortification 2019[106] ml/kg/day
AAP; ESPGHAN :Milan All preterm infants with a birth HM fortification should
Consensus 2015[113] weight <1800 grams should be fed start with standard
fortified HM fortification.
Summary of Evidence
Evidence indicates that human milk (HM) is the best form of nutrition. However, HM does not
provide sufficient nutrition for the very low birth weight (VLBW) infant when fed at the usual
feeding volumes leading to slow growth with the risk of neurocognitive impairment and other
poor health outcomes. The objective of fortification is to increase the concentration of
nutrients to try to the meet the high requirements of this group.
The recent Cochrane systematic review [103] identified 14 randomized trials in which a total of
1071 infants participated. It concluded that individual trials were generally small and had weak
methodology. Nevertheless, meta-analyses led to low-quality evidence that multi-nutrient
fortification of breast milk increases in-hospital rates of growth by a mean daily weight gain of
1.81 g/kg (with a 95% confidence interval [CI] 1.23–2.40), by a mean weekly length gain of 0.12
cm (95% CI 0.07–0.17), and by a mean weekly head circumference gain of 0.08 cm/wk (95%
CI 0.04–0.12). The meta-analyses did not show a positive effect of fortification on
developmental outcomes. There was also low-quality evidence that fortification did not

increase the risk of NEC in preterm infants with a typical relative risk (RR) 1.57 (95% CI 0.76–3.23).
In conclusion, multi-nutrient fortified breast milk compared with unfortified breast milk does not
significantly affect important outcomes, but that it leads to a slight increase of in-hospital
growth rates.
With regards to timing of commencement of fortification, recent systematic review [107] looking
into comparing early and delayed fortification included 2 studies [108,109] did not report
differences between groups including anthropometry, NEC or sepsis. In conclusion, current
data are limited and do not provide evidence on the optimal time to start fortification. Early
fortification was at 20 ml/kg/day in one group, first feeding in other group and in study by
Sullivan et al [110](which was not designed to compare EF with DF) showed that fortification with
human-milk-based fortifier was tolerated at 40 mL/kg/day. The EMBA panel
recommends Human milk fortification can be started safely with multi-nutrient fortifiers when
the milk volume reaches 50–80 ml/kg/d.[106]
With regards to exclusive Human milk based fortifiers, there is limited efficacy data and high
costs prevents its implementation in low resource settings. The OptiMoM study[112], is the first trial
comparing the efficacy of HM-based fortifier to bovine-based fortifier in the absence of
formula. There was no difference in feeding tolerance, postnatal growth and morbidity,
including NEC ≥ grade 2 ((4.7 vs. 4.9%). In one more study[110] HM-based fortifier was never
directly compared with the bovine based fortifier and many of the babies who developed
NEC on the bovine fortifier were also on the bovine formula, though this study showed a
significant reduction in NEC rates from 16 to 6% and cost-effectiveness.
RECOMMENDATION 14
• Multi-nutrient fortification of breast milk can be initiated in preterm LBW infants with
birthweight <1800 g and receiving enteral feeds of at least 50-80 mL/kg/day. For
resource limited settings, fortification may be commenced only for those infants
who fail to gain weight despite adequate breast milk feeding.
• There is limited efficacy and safety data to recommend Human milk based fortifiers.
In addition, there are ethical and cost concerns.
Weak Recommendation based on Low to moderate quality evidence
Practice Question 15: Should DHA/LCPUFA supplementation vs. No DHA supplementation be

used in LBW feeding?[114–125][126,127]
Summary of Evidence
Data from Cochrane Database of Systematic Reviews 2017[116] which included 17 RCTs (2260
preterm infants) does not indicate a long-term benefit of LCPUFA supplementation of formula
on visual development, neurodevelopment or physical growth of preterm infants.

Visual Acuity
Visual acuity was measured by Teller and Lea acuity cards in eight studies, by visual evoked
potential (VEP) in six studies and by electroretinography in two studies. Most studies found no
differences in visual outcomes between supplemented and control infants. A GRADE analysis
for this outcome indicated that the overall quality of evidence was low and meta-analysis
could not be performed.
Neurodevelopment
Meta-analysis of four studies evaluating Bayley Scales of Infant Development at 12 months (N
= 364) showed no significant effect of supplementation (Mental Development Index (MDI): MD
0.96, 95%CI −1.42 to 3.34; P = 0.43; I² = 71% - Psychomotor Development Index (PDI): MD 0.23,
95%CI −2.77 to 3.22; P = 0.88; I² = 81%). Furthermore, three studies at 18 months (N = 494) also
revealed no significant effect of LCPUFA on neurodevelopment.
Growth
Meta-analysis of four studies at a corrected age of 12 months (N = 271) showed no significant
effect of supplementation on growth outcomes (Weight: MD−0.10, 95% CI −0.31 to 0.12; P =
0.34; Length: MD 0.25; 95% CI −0.33 to 0.84; P = 0.40; Head circumference: MD −0.15, 95% CI
−0.53 to 0.23; P = 0.45).
Overall, the quality of evidence was considered low, given the small sample sizes high or
unclear risk of bias in some of the included studies and high statistical heterogeneity.
Qawasmi [126]2012 conducted a meta-analysis of 19 RCTs (12 term and 7 preterm RCTs) and
concluded that LCPUFA supplementation improves visual acuity up to 12 months of age.
However, the benefits were not statistically significant for the subgroup of preterm infant RCTs.
Beyerlein[127] 2010 conducted an individual patient data (IPD) meta- analysis of 870 infants
from four large RCTs (two preterm RCTs and two term RCTS) of LCPUFA supplementation in
formula. For preterm infants, they reported no significant differences in BSID scores at 18 months
of age between the LCPUFA and control groups (N = 341, mean difference for MDI scores 1.9,
95% CI −1.3 to 5.0; mean difference for PDI scores −0.2, 95% CI −3.2 to 2.7). There is good
evidence that supplementing DHA in formula milk at 0.32 in term babies has statistically
significant results in Visual acuity and neurodevelopment ( DIAMOND study) [117]. Effect of DHA
supplementation for role in decrease in BPD in preterm infants is not very clear. In the recent
study by Collins et al[128] Enteral DHA supplementation at a dose of 60 mg per kilogram per day
did not result in a lower risk of physiological bronchopulmonary dysplasia than a control
emulsion among preterm infants born before 29 weeks of gestation and may have resulted in
a greater risk. A total of 1205 infants survived to the primary outcome assessment. Of the 592
infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having
physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants
assigned to the control group (relative risk 1.13; 95% confidence interval [CI], 1.02 to 1.25; P =
0.02).
RECOMMENDATION 15
Routine supplementation of docosahexaenoic acid (DHA) / long chain polyunsaturated

fatty acid (LC-PUFA) is NOT recommended in preterm LBW infants.
Weak recommendation based on Low quality evidence

Practice Question 16: Should vitamin A supplementation vs. No vitamin A supplementation be

used for LBW infants?[7,129–133]
Table 4: Summary of previous guideline
Association / Recommendation Remarks

Professional body
WHO Optimal feeding Daily oral vitamin A supplementation for Weak
of LBW in low and LBW infants who are fed mother's own recommendation
middle income milk or donor human milk is not based on low quality
countries 2011[7] recommended. evidence
Summary of Evidence
Table 5: Vitamin A supplementation compared to No vitamin A supplementation for LBW infants
Anticipated absolute effects

№ of Relative
Certainty of
participants effect
Outcomes the evidence Risk with No Risk difference
(studies) (95%
(GRADE) vitamin A with Vitamin A
Follow-up CI)
supplementation supplementation
Mortality before 1
month ( 23 fewer per
RR 0.86
Intramuscular + Oral 1165 ⨁⨁⨁◯ 1,000
(0.66 to 168 per 1,000
route) (6 RCTs) MODERATE a (57 fewer to 18
1.11)
follow up: mean 1 more)
months
Mortality before 1
month - 53 fewer per
RR 0.86
Supplementation by 154 ⨁⨁⨁◯ 1,000
(0.56 to 377 per 1,000
oral route (1 RCT) MODERATE a (166 fewer to
1.33)
follow up: mean 1 124 more)
months
Chronic lung disease

51 fewer per
(oxygen use at 28 RR 0.93
1070 ⨁⨁⨁◯ 1,000
days in survivors) (0.86 to 725 per 1,000
(7 RCTs) MODERATE b (101 fewer to 7
follow up: mean 1 1.01)
more)
months
56 fewer per
Death or chronic RR 0.93
1165 ⨁⨁⨁◯ 1,000
lung disease (oxygen (0.88 to 798 per 1,000
(6 RCTs) MODERATE b (96 fewer to 8
use at 28 days) 0.99)
fewer)

Table 5: Vitamin A supplementation compared to No vitamin A supplementation for LBW infants
Anticipated absolute effects

№ of Relative
Certainty of
participants effect
Outcomes the evidence Risk with No Risk difference
(studies) (95%
(GRADE) vitamin A with Vitamin A
Follow-up CI)
supplementation supplementation
Death before 36 RR 1.00 0 fewer per 1,000

1089 ⨁⨁⨁◯
weeks' postmenstrual (0.77 to 168 per 1,000 (39 fewer to 49
(4 RCTs) MODERATE b
age. 1.29) more)
Chronic lung disease 69 fewer per

RR 0.87
(oxygen use at 36 986 ⨁⨁⨁◯ 1,000
(0.77 to 530 per 1,000
weeks' postmenstrual (5 RCTs) MODERATE b (122 fewer to 5
0.99)
age in survivors). fewer)
Neurodevelopmental
53 fewer per
impairment at 18 to RR 0.89
538 ⨁⨁⨁◯ 1,000
24 months (0.74 to 481 per 1,000
(1 RCT) MODERATE b (125 fewer to 38
follow up: mean 2 1.08)
more)
years
Cochrane review assessed the benefits and risks of vitamin A supplementation in VLBW infants
( <1500g &<32 weeks). The meta-analysis of the eight eligible trials suggested a beneficial
effect in reducing death or oxygen requirement at 1 month of age (RR 0.93, 95% CI 0.88 to
0.99) and oxygen requirement at 36 weeks postmenstrual age (RR 0.87, 95% CI 0.77 to
0.98).[131]However, of the eight studies, only one trial used the oral route for vitamin A
supplementation. (Wardle et al 2001)[134].This study did not find any significant effect on either
mortality until discharge (RR 0.86, 95% CI 0.56 to 1.33) or chronic lung disease (RR 1.0, 95% CI
0.8 to 1.24) following daily oral vitamin A supplements of 5000 IU/kg in ELBW infants. The quality
of evidence for both the outcomes was graded as low.
With regards to outcome of retinopathy of prematurity, there was a small trend to reduced
incidence of retinopathy of prematurity in the vitamin A group (typical RR 0.81, 95% CI 0.65 to
1.01). There was a marginal reduction of the combined outcome of death or chronic lung
disease (moderate-quality evidence). Although there is a statistical reduction in chronic lung
disease, these findings are consistent with either a meaningful impact on chronic lung disease
or a negligible impact. One trial that investigated neurodevelopmental status at 18 to 22
months of age correcting for prematurity found no evidence of benefit or harm associated
with vitamin A supplementation compared to control (RR 0.89, 95% CI 0.74 to 1.08) (low-quality
evidence).[132] No adverse effects of vitamin A supplementation were reported, but it was
noted that intramuscular injections of vitamin A were painful.
Evidence provided in the review by Haider et al [129] does not indicate a potential beneficial
effect of vitamin A supplementation among term neonates at birth in reducing mortality during
the first six months or 12 months of life. High-quality evidence indicates that vitamin A
supplementation in children aged between 6 and 59 months decreases all-cause childhood
mortality by 12% (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.79 to 0.98) [130] There is low
quality evidence for no benefits or harm in any of the critical outcomes with daily oral vitamin

A supplementation. In VLBW infants ( less than 1000 grams birth weight), repeat intramuscular
doses of vitamin A to prevent chronic lung disease may depend upon the local incidence of
this outcome and the value attached to achieving a modest reduction in the outcome
balanced against the lack of other proven benefits and the acceptability of the treatment to
be considered. The optimal dose appears to be 5000 IU three times weekly for four weeks.
RECOMMENDATION 16
Routine oral or intramuscular supplementation of vitamin A is not recommended in LBW

infants.
Practice Question 17: Should iron supplementation vs. no iron supplementation be used for
supplementing LBW infants?[7,135–142]
Table 6 : Summary of previous guidelines
Association / Recommendation Remarks

Professional body
WHO Optimal feeding VLBW infants fed mother’s own milk or Weak
of LBW in low and donor human milk should be given 2-4 recommendation
middle income mg/kg per day iron supplementation based on low quality
countries 2011[7] starting at 2 weeks evidence
Commentary from Prophylactic enteral iron
ESPGHAN 2010[8] supplementation should be started at 2
to 6 weeks of age in dose range of 2-3
mg/kg/day at least until 6-12 months of
age
Nutrition Committee, Recommends Iron supplementation
Canadian Pediatric Birthweight >1 kg – 2-3 mg/kg/day
Society[143] <1 kg 3-4 mg/kg/day to start at 6-8
weeks of age till 12 months of age
Summary of Evidence
Additional iron is necessary to meet the needs of erythropoiesis and growth of preterm infants.
The iron status of preterm infants receiving non-fortified breast milk starts to deteriorate within
1 to 4 months.
The Cochrane review 2012[142] looked into enteral iron supplementation in preterm and low
birth weight infants. Twenty six studies (2726 infants) were included in the analysis. Of thirteen
studies reporting at least one growth parameter as an outcome, only one study of poor quality
found a significant benefit of iron supplementation. Most studies reported a higher mean

haemoglobin in iron-supplemented infants after 2 months. Limited studies included in the

metanalysis. suggested the haemoglobin concentration in iron-supplemented infants was
higher by about 6 g/L at six to nine months. The studies comparing high and low doses of iron
indicated that there was no discernible haematological benefit in exceeding ’standard’ doses
of iron (i.e. 2 mg/kg/day to 3 mg/kg/day).
In the more recent systematic review which included recent studies McCarthy et al[135]
reported on 27 articles, and most articles (23/27) reported iron status indices. Supplementation
for more than 8 weeks resulted in increased hemoglobin and ferritin concentrations and a
reduction in iron deficiency and anemia. No article reported on iron overload. Growth-related
parameters reported in 12 articles were not affected by supplementation. Among the 7
articles on neurological development, a positive effect on behavior at 3.5 and 7years was
observed[144,145] No association was found between supplementation and adverse clinical
outcomes in the 9 articles included. Further study follow up at 12 months [146] showed Iron
supplements with 2 mg/kg/day until 6 months of life effectively reduces the risk of Iron
deficiency during the first 12 months of life.
Early versus Late supplementation (2 weeks versus 6 weeks)[136,138]

Early treatment was associated with significantly smaller decreases in serum ferritin and
haemoglobin levels (P <.001). In addition, the rate of blood transfusions was lower with early
compared with late iron supplementation (P = .022). There was no difference between early
and late supplementation in the number of patients with necrotizing enterocolitis (P = .646).
Sensitivity analysis indicated no one study overly influenced the findings and that the data was
reliable.[138]
Cumulative iron intake with early supplementation was calculated to be > 3 times of late
supplementation. A follow-up study demonstrated a lower incidence of mild motor signs and
a trend towards better cognitive function at 5 years of age in those supplemented from 2
weeks, suggesting potential long-term benefits with early supplementation.[147]The lack of long-
term neurological morbidity also supports the safety of early iron supplementation
RECOMMENDATION 17
Oral iron supplement in a daily dose of 2–4 mg/kg of elemental iron is recommended in
LBW infants from 2-4 weeks of life to 12 months of age.
Weak recommendation based on Low quality evidence

Practice Question 18: Should Probiotics vs. No probiotics be used to supplement feeding in LBW
infants?[148–159]
Summary of Evidence
Table 7: Probiotics compared to No Probiotics for feeding in LBW infants
Patient or population: feeding in LBW infants

Setting: NICU
Intervention: Probiotics
Comparison: No Probiotics
Anticipated absolute
effects
№ of
Certainty of Relative
participants
Outcomes the evidence effect Risk
(studies)
(GRADE) (95% CI) Risk with No difference
Follow-up
Probiotics with
Probiotics
26 fewer
RR 0.57
Severe NEC (NEC) 8535 ⨁⨁⨁◯ per 1,000
(0.47 to 60 per 1,000
follow up: median 2 years (29 RCTs) MODERATE a (32 fewer to
0.70)
18 fewer)
20 fewer
RR 0.88
7987 ⨁⨁⨁◯ 168 per per 1,000
Sepsis (LOS) (0.80 to
(28 RCTs) MODERATE a 1,000 (34 fewer to
0.97)
5 fewer)
15 fewer
RR 0.77
8186 ⨁⨁⨁⨁ per 1,000
Mortality (0.65 to 66 per 1,000
(27 RCTs) HIGH b (23 fewer to
0.92)
5 fewer)
In a systematic review[149] for benefits of probiotics in Low and Middle income countries looked
into NEC, Late onset sepsis and All -cause mortality outcomes
Table 8 : Systematic review of probiotics in LMIC
Outcome Absolute risk Absolute risk Number of Relative effect (RR) Quality of
Control Probiotics participants 95% CI evidence
Late-onset 358/1986 308/1986 (14.5%) 3902 0.80 (0.71 to 0.91); High

sepsis (18%) P=0.0009, I2=25%
Mortality 176/2048 137/2148 (6.4%) 4196 0.73 (0.59 to 0.9); High
(8.6%) P=0.003, I2=0%
NEC 135/1957 65/2065 (3.1%) 4022 0.46 (0.34 to 0.61); High
(6.9%) P<0.00001, I2=19%

The evidence was deemed high in view of the large sample size, low risk of bias in majority
(14/20) of the included studies, narrow CIs around the effect size estimate, very low P Value for
effect size estimate and mild statistical heterogeneity. Further meta-analysis[151] comparing
single strain probiotic versus multi-strain probiotics included a total of 25 trials (n = 7345
infants).Multiple strains probiotics were associated with a marked reduction in the incidence
of NEC, with a pooled OR of 0.36 (95% CI, 0.24–0.53; P < .00001). Single strain probiotic using
Lactobacillus species had a borderline effect in reducing NEC (OR of 0.60; 95% CI 0.36–1.0; P
= .05), but not mortality. Multiple strains probiotics had a greater effectiveness in reducing
mortality and were associated with a pooled OR of 0.58 (95% CI, 0.43–0.79; P = .0006. One more
meta-analysis[150] showed probiotics prevented NEC in preterm infants (RR 0.47 [95 % CI 0.36-
0.60], p < 0.00001). Strain-specific sub-meta-analyses showed a significant effect for
Bifidobacteria (RR 0.24 [95 % CI 0.10-0.54], p = 0.0006) and for probiotic mixtures (RR 0.39 [95 %
CI 0.27-0.56], p < 0.00001).
The above results indicate that probiotics are effective in significantly reducing the risk of all-
cause mortality, LOS and NEC in preterm VLBW neonates. Things which needs to be considered
before the local unit decides for blanket probiotic supplementation for all preterm infants :
1) Have other efforts to reduce NEC been applied in your unit? 2.) What is the baseline
incidence of NEC within your unit? 3) Is the target population in your unit similar to the
population studied in trials and implementation cohort studies? 4.) Which probiotic products
are available to your unit?
RECOMMENDATION 18
Multi-strain probiotics may be initiated in preterm low birth weight infants from as early as
day 1 of life and continued until 36-37 weeks post-menstrual age or discharge (whichever is
earlier) in neonatal units with high baseline incidence of necrotizing enterocolitis.
Weak recommendation based on Moderate quality evidence

Practice Question 19: Should Vitamin D supplementation vs. no Vitamin D supplementation be

used for supplementing LBW infants
Association / Recommendation Remarks Recommended

Professional body Vit D Serum
level
WHO Optimal VLBW infants should be given Weak
feeding of LBW in vitamin D supplements at a recommendation
low and middle dose ranging from400 i.u to based on very low
income countries 1000 i.u. per day until 6 quality evidence
2011[7] months of age.
Commentary Recommends 800-1000 IU/ Preterm infants >80 nmol/l
from ESPGHAN day
2010[8]
AAP Committee Vitamin D should be Preterm Infants >50 nmol/l
on Nutrition provided at 200 to 400 VLBW
2013[160] IU/day both during
hospitalization and after
discharge from the hospital
AAP Committee 400 IU-1000 IU / day Preterm infants >50 nmol/l
on Nutrition >1500g, tolerating
2013[160] full enteral feeds
Summary of evidence
Several studies have demonstrated that preterm infants born <32 weeks (and especially those
<28 weeks) are at greater risk of developing vitamin D deficiency compared to more mature
infants.[161,162]Approximately 10% to 20% of extremely low‑birth weight infants have radiological
evidence of rickets with metaphyseal changes despite current nutritional practices. [163]. Level
of less than 20 ng/ml (50 nmol/liter) is considered as Vitamin D deficient by professional
bodies[164] Vitamin D deficiency (serum 25-hydroxyvitamin D < 15 ng/mL) in low birth weight
infants was 87.3% in a study from India (Agarwal 2012) [165]
From the metanalysis of 12 RCT’s by Yang et al[166], there are no differences between high-
dose (800–1000 IU/d) and low-dose (400 IU/d) groups on calcium, phosphorus, and 25(OH)D
concentrations (p>.05). However, length gain and head circumference gain are significantly
increased in the high-dose group (p< .05)
In a study by Mathur et al[167] comparing 400 IU vs 1000 IU , Vitamin D supplementation in a

dose of 1000 IU/day is more effective in maintaining serum calcium, phosphate, ALP, 25-OHD
and parathormone levels with lower incidence of skeletal hypomineralization and better
growth. The mean serum 25 OHD levels increased significantly in both the groups after 6 weeks,
but were significantly higher in 1000 IU (50.91 6 11.14 ng/ml) compared with 400 IU (29.37 6
11.03 ng/ml) (p < 0.001).Another Indian trial also reported supplementation at 800 IU better
than 400 IU[168]

In the RCT[169] comparing 400 IU vs 800IU, concludes that Improvement in 25(OH)D3 levels at 4
weeks, bone density, and trends towards improvement in linear growth support consideration
of a daily dose of 800 IU of vitamin D for infants <32 weeks cared for in the NICU. Serum
25(OH)D3 levels at birth were 41.9 and 42.9 nmol/l for infants in the 400 IU group and 800 IU
group, respectively (p = 0.86). After 4 weeks of D3 supplementation, median 25(OH)D3 levels
increased in both groups (84.6vs. 105.3 nmol/l for 400 vs. 800 IU/day. respectively, with
significantly more improvement in the higher dose (p = 0.048). Infants in the 400 IU group were
significantly more likely to have dual energy x-ray absorptiometry (DEXA) bone density
measurements <10 percentile (56% vs 16%, p = 0.04).
Cho SY et al[170] demonstrated that supplementation during NICU hospitalization with 800 IU in
a cohort of infants <1500 grams showed no safety concerns with all infants having levels above
25 nmol/l but 21% of infants still insufficient at 36 weeks CGA[170]. Another trial[171] evaluating
placebo, 200 IU and 800 IU daily vitamin D supplement evaluated levels at 36 weeks and days
of respiratory support, showing prevention of vitamin D deficiency with the 800 IU dose, and
an improvement in serum levels with the 200 IU dose as compared to placebo, but no
difference in days alive or in respiratory support.
There is evidence that Preterm infants fed breast milk or formula without supplementation have
been shown in previous studies to have decreasing levels over the subsequent weeks (up to
28%) or to maintain their 25(OH)D status at suboptimal levels[172] As studies have confirmed that
relation between vitamin D3 intake and the mean circulating concentration of 25(OH)D,
additional supplementation of Vitamin D is required to reach a circulating 25(OH)D
concentration above 50-75 nmol/L.
RECOMMENDATION 19
VLBW infants should be given vitamin D supplements at a dose ranging from 400 IU to 1000
IU per day from the day of reaching full enteral feeds to 6 months of age.
Weak recommendation based on moderate level of evidence

Abbreviations
AA – Arachidonic acid AC – Abdominal circumference ALA – Alpha linolenic acid

BPD – Bronchopulmonary BSID – Bayley’s scale of infant CI – Confidence interval
dysplasia development
CLD – Chronic lung disease CMV – Cytomegalovirus DBM – Donor breast milk
DHA – Docosahexaenoic acid DHM – Donor human milk EBM – Expressed breast milk
ELBW – Extremely low birth EMPD – Electromagnetic FFM – Fat free mass
weight device
FT – Feeding tube GA – Gestational age GER – Gastro esophageal reflux
GERD - Gastro esophageal GRV – Gastric residual volume HBF – Human milk based fortifier
reflux disease
HIV – Human HM – Human milk HMB – Human milk bank
immunodeficiency virus
IUGR – Intrauterine growth IV – Intravenous IQR – Interquartile range
restriction
KMC – Kangaroo mother care LA – Linoleic acid LBW – Low birth weight
LCPUFA – Long chain LMIC – Low and middle income MD – Mean difference
polyunsaturated fatty acid countries
MDI – Mental developmental MMC – Migrating motor MOM – Mother’s own milk
index complex
NDI – Neurodevelopmental NEC – Necrotizing enterocolitis NEMU – Nose ear midway to
impairment umbilicus
NG – Nasogastric NNT – Number needed to treat NPV – Negative predictive
value
OG – Orogastric PDI – Psychomotor PN – Parenteral nutrition
developmental index
PPV – Positive predictive value PVL – Periventricular RCT – Randomized controlled
leukomalacia trial
RD – Risk difference ROP – Retinopathy of RR – Relative risk
prematurity
SCBU – Special care baby unit SGA – Small for gestational age SNCU – Sick newborn care unit
TPN – Total parenteral nutrition USG - Ultrasonography VLBW – Very low birth weight

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Clinical Practice Guidelines - Feeding of Low Birth Weight Neonates

Technical Report · January 2020

Nishant Banait Sriparna Basu

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National Neonatology Forum, India

Guideline Development Group (Alphabetical)

Nishanth Banait Ashok Kumar

Gopal Agrawal Umesh Vaidya

Editorial Board (Alphabetical)

© NNF India Online Version www.nnfi.org/cpg January 2020

The recommendations made by this group are summarized in Table 1.

NNF India Evidence-based Clinical Practice Guidelines January 2020

Table 1: Summary of recommendations for feeding of low birth weight neonates

S.No. Recommendations Strength of Quality of

2. (a). If mother’s own milk is not available, Strong, Moderate

3. Early trophic feeding started within 24 hours of life is Strong, Low

4. Stable preterm very low birthweight infants may Strong, Moderate

5. Daily feed volumes are to be increased by 30- Strong High

6. In the absence of other signs of feed intolerance in Weak Low

NNF India Evidence-based Clinical Practice Guidelines January 2020

9. Intra-gastric route of tube feeding is preferred over Weak Low to

10. Continuous feeding is not recommended as a Weak Low to

12. Checking of position of feeding tube (NG/OG) Weak, Conditional Low

14. Multi-nutrient fortification of breast milk can be Weak Low to

15. Routine supplementation of docosahexaenoic Weak Low

16. Routine oral or intramuscular supplementation of Weak Low

NNF India Evidence-based Clinical Practice Guidelines January 2020

18. Multi-strain probiotics may be initiated in preterm Weak, Conditional Moderate

19. VLBW infants should be given vitamin D Strong Moderate

NNF India Evidence-based Clinical Practice Guidelines January 2020

Scope of the guidelines and target audience

How to use these guidelines

NNF India Evidence-based Clinical Practice Guidelines January 2020

Questions relevant to clinical practice

NNF India Evidence-based Clinical Practice Guidelines January 2020

For each question, the following outcomes were considered critical

The following outcomes were considered to be important

NNF India Evidence-based Clinical Practice Guidelines January 2020

Interpretation of strong and conditional recommendations

Evidence Review and Formulation of recommendations

Data abstraction and summary tablsof individual studies

NNF India Evidence-based Clinical Practice Guidelines January 2020

NNF India Evidence-based Clinical Practice Guidelines January 2020

NNF India Evidence-based Clinical Practice Guidelines January 2020

Questions, Evidence summaries and Recommendations

Table 2: Summary of previous guidelines

Association / Professional Recommendation Remarks

NNF India Evidence-based Clinical Practice Guidelines January 2020

Strong recommendation, not graded

(b). If donor human milk is not available, formula milk is to be considered.

Strong Conditional recommendation, based on Moderate quality evidence

NNF India Evidence-based Clinical Practice Guidelines January 2020

Strong Conditional recommendation, Low quality evidence

NNF India Evidence-based Clinical Practice Guidelines January 2020

Strong Conditional recommendation, Moderate quality evidence