1. Systematic review: feeding practices for LBW infants in LMICs
Abimbola Akindolire

2. Background
Survival of small and very small babies have improved over the last 20 years.
A large majority of preterms at term gestational age are growth restricted
The main consequence of this growth restriction is reduced brain growth leading to cognitive delays.
To prevent this, adequate nutrition must be started as early as possible.
New research into best feeding practices in order to how to achieve the same intrauterine growth rates
Most available research/reviews are from the HICs and current guidelines are based on these information
Mortality rates for preterm neonates have reduced in the last 20 years, survival of small and very small babies have improved
Survival of small and very small babies have improved over the last 20 years.
A large majority of preterms at term gestational age are growth restricted because for many reason they have not had enough protein and energy required for their growth.
The main consequence of this growth restriction is reduced brain growth leading to cognitive delays.
To prevent this, adequate or complete nutrition must be started earlier or age appropriate nutrition given.
New research into nutrition and how to achieve the same growth rates as for babies growing in their mother’s uterus.

3. Literature search
A literature search was conducted to see what evidence is available from LMICs to base current feeding practices on
The questions we were asking at this time were
What to feed
How to feed
When to start feeding
How to advance

4. Literature search- what to feed Reviews comparing formula milk to human milk
Henderson et al in 2007 compared formula milk and maternal breast milk
The outcomes of interest were the effects on growth & development and morbidity & mortality
No randomized control trials were found
Henderson et al in 2007 compared nutrient enriched formula milk and human breast milk post-discharge
The outcome of interest were the effects on growth & development, bone mineralization, feed intolerance, BMI and blood pressure on follow up

5. Literature search- what to feed Review comparing formula milk to donor human milk
Quigley 2014
9 studies -Europe 5, USA 3, Europe &USA 1; 5 studies term formula vs donor human milk and 4 studies preterm formula vs human donor milk
1070 babies- <1,800gm/32 weeks
Outcomes of interest were effects on
Growth & development.
Incidence of adverse effects such as death, NEC, invasive infection and feed intolerance.
Days to full feed.
Quality of evidence was weak
Main findings were increased short-term growth with formula but no effect on post-discharge growth or developmental outcomes. There was increased risk of NEC and feed intolerance in the formula fed population
Quality of evidence was weak: uncertainty about concealment of allocation methods and lack of blinding
Need more studies comparing preterm formula with human milk

6. Literature search Reviews on breast milk fortification
Many reviews in HICs
Most show evidence of improvement in weight gain with fortification

7. Europe 5, N. America 4, Asia 3, South Africa 1071 <2Kg
Author, year
No. of studies
Setting
No. of children
Comparison
Outcomes
Quality of evidence
Conclusion
Brown 20161 14
Europe 5, N. America 4, Asia 3, South Africa
1071
<2Kg
Multinutrient fortified human milk vs unfortified human milk
Growth & development
Weak
Limited data Improved in-hospital growth
Kuschel 2000 1
Sweden
Supplementation of human milk with fat/MCT vs unsupplemented human milk
Growth & neurodevt. outcomes at months. GI dist., feeding intolerance, diarrhoea, NEC
Small numbers
Insufficient data
Young 20132 2
Canada & Denmark
246
Multinutrient fortification of human milk vs unfortified human milk post-discharge for 3-4 months
Growth & devt. Duration of B/feeding. Bone mineralization. Rickets. Feed intolerance. Blood pressure on follow up
Good but small numbers
Limited data
Europe 5, N. America 4, Asia 3(India & Oman), South Africa
Limited data – no strong evidence of effect of fortification on important outcomes. Improved in-hospital growth
No significant difference in short term growth. Insufficient data to make recommendation
Limited data does not provide evidence of effect on important outcomes in infancy.

8. Literature search Reviews comparing different types of formula feeds
Author, year
Setting N
Comparison
Outcomes
QOE
Conclusion
Basuki, 20137
3-USA 2, India 1
102
Dilute vs full strength in exclusively formula fed preterm
NEC, wt gain. Feed tolerance, time to full feeds, LOHS
Low to moderate quality
Less feed intolerance less time to full feeds in the dilute strength. NEC not reported.
Fenton 20148
6-USA 3, UK 1, Netherlands 1, Sweden 1
244
Higher (≥3g/kg/day but <4g/kg/day) vs lower (<3g.kg.day) protein in formula fed preterm or LBW infants 5 studies and 1 study with very high (≥4g/kg/day) vs high(≥3g/kg/day but <4g/kg/day
Growth, BUN, IQ, abnormal phenylalanine levels, growth failure. Feed intolerance, days to full feed, NEC, sepsis, diarrhoea, metabolic acidosis
Weak
Higher protein intake accelerates weight gain but limited data on long term outcomes. Insufficient evidence to make recommendations for very high protein formula.
Little information on information on allocation method or blinding. Heterogeneity in formulas tested, and characteristics of infants may explain differences in treatment effects

9. 17-Mainly Europe, USA and Canada, multicentre 2, Taiwan 1 2,260
Moon 20169
17-Mainly Europe, USA and Canada, multicentre 2, Taiwan 1
2,260
Longchain PUFA enriched formula vs standard formula
Visual development, neurodevelopment, growth
Low
Pooling of results showed no clear longterm benefits or harms of the intervention
Nehra
8-USA 5, Netherlands 2, Canada 1
182
High vs low medium chain triglyceride content formula
Short term growth, neurodevelopment, longterm growth
Little info on allocation method or blinding
No evidence of difference in short term growth.
Young
16 Most in Europe, USA. 1 -S. Korea, Israel and Taiwan
1,251
Nutrient enriched vs standard formula post-discharge
Growth, devt. Feed tolerance Bone mineralization BMI, Bp.
Moderate
Limited evidence that use of preterm formula post-discharge may increase growth up to 18 months.
2. No evidence of difference in short term growth. Long term outcomes in growth and neurodevelopment were not reported. No evidence of effect of NEC- larger studies are needed
3. Limited evidence that use of preterm formula post-discharge may increase growth up to 18 months. Not enough evidence to recommend routine

10. Literature review- When to start feeds
Morgan, 2013, Trophic feeds vs fasting
Primary outcomes
Feed intolerance: days to establish full enteral feeding independently of parenteral nutrition.
Necrotising enterocolitis
Secondary outcomes 
All-cause mortality prior to hospital discharge.
Growth
Neurodevelopment
Incidence of invasive infection
Duration of phototherapy for hyperbilirubinaemia (days).
Duration of hospital stay
Delayed introduction or notM
Trophic feeding (also referred to as minimal enteral nutrition, gut priming and hypocaloric feeding) was developed and adopted into clinical practice as an alternative to complete enteral fasting for very preterm or VLBW infants during the early neonatal period (Klingenberg 2012). Early trophic feeding is conventionally defined as giving small volumes of milk (typically 12 to 24 ml/kg/day) intragastrically starting within the first few days after birth, without advancing the feed volumes during the first week postnatally (McClure 2001). The primary aim of trophic feeding is to accelerate gastrointestinal physiological, endocrine and metabolic maturity and so allow infants to transition to full enteral feeding independent of parenteral nutrition more quickly. However, any beneficial effects may be negated if early trophic feeding increases the risk of necrotising enterocolitis in very preterm or VLBW infants.

11. Author Year N, Type of babies Country Intervention Ostertag 1986
North America
>day4- day 7
Khayata
1987
12, <1500g
Day 10 after birth
Davey
1994
62, <2000g
>Day4- day 7
Karagiami
2010
84, <35 weeks
Greece
Pevez
2011
239, <1500g
Colombia
Abdulma aboud
2012
125, <1500g
Qatar
Leaf
54, <35weeks
UK/Ireland
Armanian
2013
82, <1500g
Iran
Arnon
60, SGA Preterms
Israel
754 infants, VLBW or <32 weeks No significant risk of NEC, No significant reduction in time to full enteral feeds

12. Literature search- How to advance
Recommended is 30ml/kg/day
What do we practice? Intuition or recommendation?
Oddie, 2017 looked at if daily increments of 15 to 20 mL/kg (compared with 30 to 40 mL/kg) reduces the risk of NEC or death in very preterm or VLBW infants, extremely preterm or ELBW infants, SGA or growth-restricted infants, or infants with antenatal AREDFV
A total of 3753 infants from 10 studies

13. Authors Year weight Setting Intervention Rayyis 1999 <1500
N. America
15 vs 35
Caple
2004
20 vs 35
Salhotra
<1250
India
15 vs 30
Krishnamurthy
2010
20 vs 30
Karagol
2013
Turkey
Raban
2014a
<1001g
S Africa
24 vs 36
2014b
<1001
Modi
2015 vs
SIFT
2016
<1500g
UK/Ireland
18 vs 30
Jaih
s 30
SIFT had 75% of the participants

14. Literature search- How to advance
Slow advancement does not reduce the risk of NEC on All and all the subgroups
Formula fed - Rayyis 185 infants, 1 study
Infants who were at least partially fed with human milk- 9 studies, 3557 infants
Extremely preterm/ELBW- 5 studies, 1299 infants
Infants with IUGR- 2 studies 639 infants
Infants with absent/ reversed end diastolic flow velocity- 2 studies, 465 infants.
Mortality- no effect on risk of mortality on all infants and all subgroups
Infants who had fast advancement achieved full enteral feeds and regained birth weight faster than those in the slow group
Incidence of LOS was higher in the slow advancement group
No conclusive evidence on length of hospital stay
Quality of evidence was moderate downgraded from high because of lack of blinding

15. Literature search- How to feed
Continuos vs bolus
Push vs gravity
NG vs OG
Bottles??

16. How to feed-Nasal versus oral route for placing feeding tube
Watson et al, studies
Van someren 1984, 42 babies, 30 to 34weeks Apnoea, Weight gain- no difference
Dsilna, <30 weeks/<1200 time to full enteral feeds and regain birth weight and incidence of adverse events
Bohnhurst 2010, 35
No significant differences in adverse events time to independence from supplemental oxygen,  time to full enteral feeds time to full oral feeds not reported
Statistical significant difference in weight gain in NG 0.6vs OG 8.3g/kg/day in 1st week none after
Data not sufficient for policy
Decision based on clinicians preference
A large RCT needed to compare

17. How to feed- Continuous versus bolus
Shahirose 2011,
7 RCTs, 511 preterm infants less than 1500gmi
No significant difference in growth and incidence of NEC but earlier discharge in ELBW fed by continuous nasogastric feeding
Quality of evidence is weak

18. How to feed- Push versus gravity
Dawson 2013, looked at the evidence that gravity feeding results in a more rapid establishment of full gavage feeds without increasing adverse events in preterm or low birth weight, or both, infants who require intermittent bolus tube feeding
Only one small trial- N 31,<32 weeks
No significant difference in heart rate at completion of feeds
Difficult to conclude
Nurses, what’s the experience

19. WHO Recommendations on optimal feeding of very low- birth- weight infants
What to feed?
Choice of milk
Mother’s milk*, Donor human milk**
Standard formula but if they fail to gain weight -Preterm formula
No routine human milk fortifiers except they fail to gain weight
Supplements
ALL- Vitamin D
On human milk-Calcium, phosphorus- unclear for how long; iron from 2 weeks-6 months

20. WHO Recommendations on optimal feeding of very low- birth- weight infants
Daily vitamin A is not recommended due to lack of evidence
When and how to initiate feeding
1st day of life 10ml/kg the remaining fluid requirement should be by IV Fluid
How to feed?
Not clearly how to feed just that in VLBW who need intragastric tube it should be by oral/nasal route
How to advance
Up to 30ml/kg/day careful monitoring for feed intolerance

21. THANK YOU FOR LISTENING