Symposium 3. Pre-term Infant in the First Week of Life

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1 Symposium 3 Fl id d N t iti S t f th Fluid and Nutrition Support of the Pre-term Infant in the First Week of Life

2 The choice of lipid in the preterm infant practice and controversy Susan Hill Department Gastroenterology Great Ormond Street Hospital for Children, London

3 Introduction History Intralipid Essential fatty acids Lipid metabolism Special needs of the neonate Newer lipid emulsions

4 PN available 40 years 1628 William Harvey 1656 Sir Christopher Wren Infusions via a bladder & sharpened quill in dogs E s Es + glucose 1930 s Robert Eltman: amino acids as a protein hydrolysate

5 BUT i-v lipid needed for High energy content Prevent lipogenesis from glucose Co2 produced exacerbating resp failure PN was not considered viable until intralipid was invented

6 P N 1960 s fat developed Problems Toxicity of low mol wt TGs Cotton seed oil: only toxic >4 weeks Solution Soya bean oil Wretlind & Schuberth 1963 Wretlind A. Fat emulsions. In Lee HA(ed) Parenteral nutrition in acute metabolic illness. Academic Press, London.1974pp77-92.

7 Intralipid Long-chain triglyceride (LCT) soya bean emulsion + egg-derived phospholipid LCT=16-20 C atoms hydrolysed by LPL cleared by Apo lipoprotein E and LDL receptors Carnitine dependent transport into cells

8 Lipid emulsion size matters Particles need to be small enough to fit through capillary <400 nm (0.4μm) Destabilised by >Ca, Mg; < fat volume; >acid:base aa s Stabilised by > glucose

9 How is lipid held in solution by egg lecithin? Fat emulsion formed by a prolonged process of homogenisation Chylomicron-like lik structure t Fat particles separated by negatively-charged g tails of phospholipid (egg lecithin) i.e. charge repulsion maintains the emulsion

10 Carnitine dependent transport into cells fatty acids are activated in cytosol & transported into mitochondria must move into mitochondria i for oxidation to occur uses carnitine as a carrier via carnitine shuttle

11 Lipid conc w/v Energy concentration lipid vs glucose (commercial lipid emulsions) Vl Volume Approx volume Approx Glucose (ml) energy energy conc w/v (kcal) (kcal) 10% % % % % % %

12 Lipid intake what to give 25-40% of non-protein calories in total PN feeding Infancy: max lipid id oxidation at 4g/day as long as 18g glucose/kg/day (or exceed oxidative capacity for CHO and net lipogenesis occurs)

13 How to give Continuous infusion Maximum 20 hours Limit 2-3 days/ week if long-term Carnitine? Consider in infants on PN >4 weeks ESPGHAN

14 Preterm infant Unpredictable fat utilisation and clearance Low plasma carnitine deficiency of taurine or cysteine

15 Complications liver disease Prematurity liver disease Low birth weight Sepsis Duration of PN use Short gut syndrome Multiple surgical procedures Absence of enteral feeds steatosis Cirrhosis cholestasis Gall stones

16 Lipid monitoring Plasma triglyceride id (TG) levell Serum bilirubin level Liver function testst Stop lipid id for 4 hours pre-test t

17 Essential fatty acids

18 Essential fatty acids what are they? Linoleic acid (LA) -> arachidonic Omega-6 α-linolenic acid (ALA) ->eicosapentaenoic (EPA) ->docosahexaenoic acids(dha) Omega-3 Neonate 0.25g/kg 0.5g/kg/d intralipid MINIMUM

19 Why are EFA s essential? synthesis of prostaglandins help regulate aspects of metabolism blood viscosity, inflammatory processes blood cholesterol fat levels water balance

20 Essential fatty acids (EFA) physiologic processes skin cell membranes synthesizing important biologically active compounds prostaglandins and leukotrienes. development of normal development of normal vision (animal studies) neurologic complications Numbness weakness inability to walk leg pain blurred vision

21 What is EFA deficiency? Depression Cardiovascular Disease Type 2 Diabetes Fatigue Dry, itchy skin Brittle hair and nails Inability to concentrate Joint pain

22 Essential fatty acids Stored in cell membranes Ratio omega 6:omega 3 2:1 up to 4:1 recommended average ratio population 10:1 even 15:1

23 Essential fatty acids Ratio ω6 :ω3 15:1 2:1 4:1 omega 6 omega 3 pro-inflammatory Anti-inflammatory grains, vegetable oils, poultry, eggs cold water oily fish green leafy vegetables walnuts

24 22/09/06 Latest News CAVEMAN HEALTH PLAN LAUNCHED BY GLASGOW DOCTOR unhealthy Brits..look at diet try and eat more like cavemen Essential Health Clinic measures levels of the vital essential fatty acids Omega 3 & Omega 6 in bloodstream. It is thought that in the days of cave men ratio of polyunsaturated Omega 3:Omega 6 EFAs in the blood stream was roughly equal. balanced each other out to contribute equally to immune response, blood clotting, oxygen transport, kidney function, healthy joints and skin.. High fat in modern diets

25 Ratio ω6 :ω3 Influences type of mediator released from WBCs via altering available precursor for fatty acids Leukotriene (LT)B4: LTB5 proinflammatory: anti-inflammatory i t LTB4 supports immune system in hyperinflammatory state Hospital stay reduced in adult surgical patients Schulski et al Clin Nutr 1999

26 Lipid preparations

27 How many lipid preparations? Soya Intralipid Olive oil Clinoleic (Olive oil + soybean oil 10%) Structured lipids (MCT/LCT) Fish oil omegaven Mixed SMOF Soya coconut Olive oil Fish oil

28 What are they? Soya/LCT efa arachidonic acid Omegaven Efa Olive oil/mufa Oleic acid <peroxidation Coconut oil/mct not carnitine dependent

29 Intralipid/soya bean oil disadvantages > ω6 6linoleic l i acid :pro-inflammatory i t effect (polyunsaturated fatty acid) < vitamin i E > peroxidation < antioxidant capacity -> immune suppression phytosterols

30 SMOF S oyabean oil M edium chain triglycerides O live oil F ish oil

31 SMOF 2g/kg Improved liver function > rapid elimination from bloodstream < triglyceride half life Probably due to > mct content Optimal LCT content ESPEN 2006 Goulet

32 SMOF trial SMOF 20% vs intralipid 20% 53 premature babies bi (26 SMOF:27 intralipid) id) <34 weeks gestation (mean 30 weeks) Birth weight g weight at start: SMOF 1.36kg intralipid 1.3kg treated 7-14 days mean age at start SMOF 6 days, intralipid 6.3 days Single centre randomised double-blind controlled trial Rayyan M FRANC Ped2007

33 SMOF trial SMOF 20% vs intralipid 20% Safety criteria Serum triglycerides Haematology Biochemistry Adverse events Tolerability Vital signs Efficacy criteria Days to regain birth weight Body weight Body height Mechanical ventilation

34 Treatment t SMOF trial SMOF 20% vs intralipid 20% Lipid introduction day 1-3: 1g/kg/day day 4: 2g/kg day day 5: 3g/kg/day Mechanism of action Plasma fatty acid profile Red blood cells phospholipids day 6-14: 3.5g/kg/day

35 Results SMOF trial SMOF 20% vs intralipid 20% Serum triglycerides SMOF mmol/l Intralipid mmol/l Haematology Biochemistry i Adverse events SMOF 5:intralipid 7 (possiby drug related) Death due to prematurity SMOF 1:intralipid2 Tolerability Vital signs

36 SMOF trial SMOF 20% vs intralipid 20% Conclusion Safe and effective Reduces ω6: ω3 May benefit brain and retina at time of May benefit brain and retina at time of rapid development

37 Omegaven fish oil Case 1, 34 week gestation male Intra-uterine mid-gut volvulus + gastroschisis 22cm dilated duodenum STEP procedure -> 52cm PN By 6 weeks: cholestasis, steatosis, bile duct proliferation, By 6 months: portal-portal bridging fibrosis Listed for small bowel transplant mild fibrosis Gura K et al PEDIATRICS 118; 2006

38 Omegaven fish oil Case 1 Omegaven 0.2g-1g/kg/day 11 hour cycled PN 2.5g/kg/day g protein + 15% dextrose. + Breast milk 15ml/hour over 24 hours Aged 15 months: thriving ; normal dvt Aged 15 months: thriving ; normal dvt cholestasis resolved < 60 days

39 25 weeks, 850g Omegaven fish oil Case 2 Terminal ileum: perforation+ fibrous adhesions aged 6 weeks Total PN >liver enzymes, >prothrombin time, < platelets Omegaven 0.5g/kg/d. Total PN Aged 4 months: normal liver function Gura K et al PEDIATRICS 118; 2006

40 Omegaven Gura K unpublished 18 further patients 1g/kg/day omegaven no adverse effects Bilirubin returned to normal 66 days vs 478 days p< BUT historical controls >ω-3 in phospholipids

41 Lipids efa Can they be given as an enteral supplement? Yes walnut oil (Salmon, flax seeds)

42 Conclusion: Lipid in PN Source of essential fatty acids and vitamin i E Concentrated energy source Isotonic Protects t photodegradation d ti of vitamin i A Prevents essential fatty acid deficiency Essential for survival

43 What to give and why Long chain efas essential BUT Balance with shorter chain fats Vitamin E Sufficient fat to enable growth Sufficient fat to enable growth that Does least harm

44 Where are we today? Soya bean is a tried and tested safe fat source BUT liver disease and sepsis improved ω 3: ω 6 with fish oils likely to improve outcome

Omega-3 fatty acids in clinical nutrition

Omega-3 fatty acids in clinical nutrition Alastair Forbes With thanks to Jon Shaffer, UK and many ESPEN colleagues Omega-3 fatty acids in clinical nutrition Review of lipids in nutrition Why and how lipids