1. Nutritional support in NICU/PICU A Norouzy Assistant Professor in Clinical Nutrition Mashad Medical School

2. Objectives Define basic nutritional requirements for neonatal growth Describe specific nutritional problems faced by low birthweight and premature infants Determine components of TPN and be able to write fluid orders Formulate an individualized plan for starting and advancing parenteral/enteral feeds

3. Goals of Nutrition To achieve a postnatal growth at a rate that approximates the intrauterine growth of a normal fetus at the same post-conceptional age Provide balance in fluid homeostasis and electrolytes Avoid imbalance in macro-nutrients Provide micro-nutrients and vitamins

4. Fetal nutrition Parenteral (mostly!) Stores are laid late in gestation At 28 weeks, a fetus has: – 20% of term calcium and phosphorus stores – 20% of term fat stores – About a quarter of term glycogen stores

5. Adaptation to nutrition after birth Gut adaptation is regulated by – Endocrine factors – Intraluminal factors – Breast milk hormones and growth factors – Bacteria

6. Normal output Daily stool and urine output guidance Day 01 wet nappy and meconium at least once a day Day 12 wet nappies and meconium at least once a day Day 2 & 33 or 4 wet nappies and changing stools at least once a day Day 4+5 or 6 heavy wet nappies and yellow stools at least once daily A baby who is passing meconium at 3 or 4 days old may not be getting enough milk. A baby who does not have yellow stools by day 5 may not be getting enough milk. A baby who is not doing as many wet nappies each day as expected may not be getting enough milk. 61394norozy dr

7. Nutrition for the preterm or sick baby

8. So how to feed? Delay start? Use non-nutritive feeds? Increase slowly? Use friendly bacteria?

9. Cochrane review: early vs late feeding 72 babies in 2 studies Early feeders had – Fewer days parenteral nutrition – Fewer investigations for sepsis No difference in – NEC – Weight gain

10. Cochrane review: rapid vs slow increase 369 babies in 3 studies Rapid: 20 to 35 ml/kg/day Slow: 10 to 20 ml/kg/day Rapid group: – reached full enteral feeds and regained birthweight faster – No difference in NEC rate or length of stay

11. Cochrane review: minimal enteral nutrition 380 babies in 8 studies 12 to 24 ml/kg/day for 5 to 10 days MEN group – Faster to full enteral feeds – Shorter length of stay – No difference in NEC

12. Probiotics for preventing NEC Systematic review of 1393 VLBW infants treated with a variety of organisms Reduced risk of – NEC (RR 0·36, 95% CI 0·20–0·65) – Death (RR 0·47, 0·30–0·73) Achieved full feeds faster No difference in rates of sepsis – Deschpande et al, Lancet 2007

13. Feeding small or preterm infants: Choices Human milk – Mother’s own – Banked donor milk – Fortified Artificial – Term formula – Preterm formula Parenteral Nutrition

15. If an infant can’t, won’t or shouldn’t be fed enterally What’s in the bag? – Fluid – Carbohydrate – Protein – Fat – Minerals and Trace Elements

16. Energy Requirements – Basal metabolic rate – Physical activity – Specific dynamic action of food – Thermoregulation – Growth

17. Energy Requirementskcal/kg/day – Basal metabolic rate40 – Physical activity4+ – Specific dynamic action of food(10%) – Thermoregulationvariable – Growth70 (To match in-utero growth of 15g/kg/day)

18. Protein With glucose infusion alone, infants lose 1- 2% of endogenous protein stores daily 1g/kg/day gives protein balance 2.5 to 3.5g/kg/day allows accretion – nb energy requirement Safe to start soon after birth

19. Fat Energy source Essential fatty acid source (intralipid) Cell uptake and utilisation of free fatty acids is deficient in preterm infants Start at max 1g/kg/day, increasing gradually to 3g/kg/day (less if septic)

20. Benefits of PN Earlier, faster weight gain Avoidance of problems associated with enteral feeds

21. Risks of PN Line associated sepsis Line related complications (eg thrombosis) Hyperammonaemia Hyperchloraemic acidosis Cholestatic jaundice Trace element deficiency

22. Milk Feeds

23. Human milk advantages Protection from NEC Improved host defences Protection from allergy and eczema Faster tolerance of full enteral feeds Better developmental and intellectual outcome

24. Human milk shortcomings if preterm Human milk may not provide enough – Protein – Energy – Sodium – Calcium, phosphorus and magnesium – Trace elements (Fe, Cu, Zn) – Vitamins (B 2,B 6,Folic acid, C,D,E,K)

25. Breast milk fortifiers Improved – short term growth – nutrient retention – bone mineralisation Concerns – trend towards increased NEC

26. Term vs preterm formulas Term formulas do not provide for preterm protein, calcium, sodium and phosphate requirements, even at high volumes Term formula (vs preterm formula) fed infants – Grow more slowly – Have lower developmental score and IQ at follow up

27. Feeding preterm infants: aim “To provide nutrient intakes that permit the rate of postnatal growth and the composition of weight gain to approximate that of a normal fetus of the same gestational age, without producing metabolic stress” American Academy of Pediatrics Committee on Nutrition

28. Evidence Based Nutrition RA Ehrenkranz, Seminars in Perinatology 2007 (31): 48-55 281394norozy dr

29. Catch-up Growth Enhanced nutritional intake sufficient to allow ‘catch-up’ growth improves long term neurodevelopmental outcome

30. Body composition differences Compared to term infants, ex-preterm infants fed at 120 kcal/kg/day – Have more body fat – Have a different fat distribution

31. Developmental Origins theory Humans demonstrate ‘developmental plasticity’ in response to their environment Part of cardiovascular risk may be explained by in-utero and postnatal growth

32. Developmental Origins theory Geographically, coronary heart disease correlates with past neonatal mortality In epidemiological studies, adult cardiovascular disease is associated with: – low birthweight – rapid early postnatal growth

33. Nutrition Assessment

34. How best to assess growth and nutrition? Weight – Reflects mass of lean tissue, fat, intra- and extra- cellular fluid compartments Length – More accurately reflects lean tissue mass Head circumference – Correlates well with overall growth and developmental achievement

35. Laboratory assessment TPN requires regular monitoring of acid base status, liver function, bone profile and electrolytes In enterally fed infants, monitoring albumin, transferrin, total protein, urea, alkaline phosphatase and phosphate may be useful

36. Complication of TPN Infiltration under skin Infection Liver dysfunction Renal overload

37. Feeding development Swallowing first detected at 11 weeks Sucking reflex at 24 weeks Coordinated suck-swallowing not present till 32-34 weeks Swallowing to coordinate with respiration – Respiration>60-80 NG feeding – Respiration>80 high risk for aspiration (NPO)

38. Methods of feeding Oral feeding – >32 weeks – Respiration<60-80 – Try 20 minutes Naso-gastric (NG) feeding bolus NG feeding continuous trans-pyloric Gastrostomy feeding

39. Trophic Feeding Keeping infant fasting (NPO) – Decrease in intestinal mass – Decrease in mucosal enzyme – Increase in gut permeability Trophic feeding: – small amount of feeding to prepare the intestine – release enteric hormones, better tolerance to feeds

40. Case A 26 week female is born precipitously to a healthy 20 year old G1P1 with an uncomplicated pregnancy. The baby is transferred to the NICU where a UAC and UVC are placed. You are getting ready to order fluids for this baby. What is your goal growth for this infant? What is this infant’s caloric requirement? What fluids do you order?

41. Gastrointestinal Development Fetal swallowing, motility in 2 nd trimester – 18 week fetus swallows 18-50ml/kg/day – Term 300-700ml/day – Fetal swallowing regulates the volume of amniotic fluid and controls somatic growth of the GI tract Intestines double in length from 25-40 weeks Functionally mature gut by 33-34 weeks Intestine in final anatomic position by 20 weeks Premature Infant GI tract: – Delayed gastric emptying seen in preterm Breast milk, glucose polymers, prone positioning facilitate gastric emptying – Total gut transit time in preterm 1-5 days – Stooling delayed until after 3 days –  feeding volume  ’s motility

42. Growth – General Facts Last trimester of pregnancy – Fat and glycogen storing – Iron reserves – Calcium and phosphoruos deposits Premature babies more fluid (85%-95%), 10% protein, 0.1% fat. – No glycogen stores The growth of VLBW infants lags considerably after birth

43. Growth Goals Weight: 20-30 g/day Length: ~1cm/week HC: 0.5cm/week – Correlates with brain growth and later development

44. Caloric Requirements for Growth Preterm goal: ~120kcal/kg/day Term goal: ~110kcal/kg/day Total Fluid of enteral feeds required to deliver adequate calories for growth is ~150cc/kg/day

45. Total Parenteral Nutrition Determine fluid requirement (mL/kg/day) for first day of life Full-term infants: 60–80 mL/kg/day Late preterm and preterm infants (30–37 weeks): 80 mL/kg/day Very-preterm infants: 100–120 mL/kg/day Determine Glucose Infusion Rate (GIR) GIR: (% dextrose x IV rate ) ÷ (6 x wt in kg) Calculate GIR from known dextrose concentration (%). Example: An infant weighs 2 kg and is receiving 100 ml/kg/day of dextrose 15% solution. – IV rate: 100 × 2 = 200 ml/day ÷ 24 = 8.3 ml/hr – GIR: (15% x 8.3 x 0.1667) ÷ 2 = 10.3mg/kg/min (15% x 8.3 ) ÷ (6 x 2) = 10.3 mg/kg/min

46. Total Parenteral Nutrition Protein and amino acids Start with 2- 3 g/kg/day – Increase 0.5–1.5 g/kg/day to a total of 3–4 mg/kg/day Goal for premature infants: 4g/kg/day Goal for term infants: 3g/kg/day Source: trophamine Calculate electrolytes to add to bag DOL#1: dextrose in water with no eletrolutes is usually appropriate except in premies with low Ca stores who may require Ca DOL#2: add electrolytes to the bag based on estimated daily requirements and BMP – Estimated Needs: NaCl = 2-4 mEq/kg/day KCl = 1-2 mEq/kg/day (NOTE: Do not supplement K until UOP >1cc/kg/hr, especially in premies) CaGluconate =200-400mg/kg/day (NOTE: mg not mEq and Ca cannot be infused at >200mg/kg/day through a central line)

47. Total Parentral Nutrition Other added nutrients Lipids Cystein Phosphrous Magnesium Trace Minerals MVI Heparin

48. Total Parenteral Nutrition Central TPNPeripheral TPN Easy to meet nutrition needs No limits on osmolarity Little risk of phlebitis Long term use May require general anesthesia Greater risk of infection Increased cost Greater risk of mechanical injury, air embolism, venous obstruction – Unable to meet needs for Ca/Phos needs – Maximum rate of Calcium gluconate is 200mg/kg/d – Maximum % dextrose is 12.5% – Short term use – Less risk for catheter related infections – Lower cost ? – Less risk of mechanical injury, air embolism, venous obstruction

49. Enteral Nutrition Breast milk is best! The American Academy of Pediatrics (2005) recommends breastfeeding for the first year of life. Started when an infant is clinically stable Absence of food in the GI tract produces mucosal and villous atrophy and reduction of enzymes necessary for digestion and substrate absorption Trophic hormones normally produced in the mouth, stomach, and gut in response to enteral feeding are diminished. Breastmilk and standard infant formula have 20kcal/30cc (30cc=1oz) Specialized formulas and fortifiers allow caloric content to be increased

50. Breastmilk Preferred source of enteral nutrition Very well tolerated by most infants Improves gastric emptying time Matures the mucosal barrier Promotes earlier &  appearance of IgA Vastly  ’s incidence of NEC More significant induction of lactase activity compared to formula fed premies Composition: – Varies with gestation – Varies according to maternal diet – Varies within a feeding(  fat in last ½ fdg) – Varies within the day(  fat in PM over AM)

51. Enteral Nutrition in the NICU Term: – If clinically stable, start PO ad lib feeds and advance as tolerated Preterm – Feeds are often initiated with breastmilk, Sim 20 or 30cc/ 24h – Trophic tube feeds may be continuous or bolus and advanced gradually (10-20mL/kg/day) – Transition to bolus from continuous typically begins after achieving full feeds – PO feeds typically attempted around 32-34 weeks, when premies develop suck and swallow coordination – Premies are often supplemented with TPN as they work up on feeds – Goal discharge formula is Neosure 22

52. What to Feed?

54. NICU

55. Energy and protein goals: TPN Term: – Energy: 80-100 kcal/kg/day – Protein: 2.5-3.5 g/kg/day Pre-term: – Energy: 90-100 kcal/kg/day – Protein: 2.5-3.5 g/kg/day

56. Energy and protein goals: enteral Term: – Energy: 108 kcal/kg/day – Protein: 2.2 g/kg/day Pre-term: – Energy: 120 kcal/kg/day – Protein: +3 g/kg/day

57. IV Lipids Preterm infants can develop EFA deficiency within 72 hours of birth Dose: 0.5-1 g/kg/day to achieve 3 g/kg/day maximum 60% of total energy

58. Amino Acids Start 1.5-3 g/kg/d Advance: 0.5-1 g/kg/d Goal: 2.5-4 g/kg/d Monitor: renal function, albumin

59. Dextrose <1000 g: glucose infusion rate: 4-6 mg/kg/min 1000-1500 g: GIR: <8 mg/kg/min GIR goal: <12 mg/kg/min GIR>14: converts CHO to fat in liver

60. Vanilla TPN order Start with amino acids ASAP Dextrose: 8-18 g/kg/d AA: 1.5-3 g/kg/d Fat: 0.5-1 g/kg/d Calcium: 150-200 mg/kg/day Phosphorous: 0.3-0.5 mmol/kg/d MVI & trace elements

61. Tapering TPN/PPN Start from lipids Keep AA until last

62. Enteral nutrition BMF or formula Trophic feed or full feed

63. Barriers and Challenges of Nutrition Support Metabolic vs nutrition support Wasting specific lesions (pre-operative nutritional status) Hemodynamic instability Severe hypotensive gut Fluid restriction Enteral vs parenteral Philosophy nutrition support will do more harm than good in immediate post-operative period Urgency to remove central line

64. Too Little vs Too Much Diamond 1995

65. Too Little vs Too Much Sedation Paralysis Intubation/ventilation + inotropes + wasting

66. Determining Caloric Requirements

67. Tools Used for Determination Indirect calorimetry Underlying disease process Biochemistrys and nitrogen balance Published papers (reference charts) Nutritional status

68. Route of Administration: Enteral vs Parenteral Indications for TPN: SBS Ileus Severe dysmotility NEC Unable to provide adequate support with enteral nutrition The gut can be used in critical illness

69. Journal of Pediatric Gastroenterology and Nutrition. 41: S1-S4

70. TPN initiation dependent on age, size, nutritional status, disease, surgery or medical intervention In small preterm infants starvation for 1 day may be detrimental Older children can wait up to 7 days dependent on circumstance Journal of Pediatric Gastroenterology and Nutrition. 41: S1-S4 Espghan Guidelines

71. Enteral: Enteral Nutrition Advantages: Decreased cost Decreased metabolic abnormalities Decreased infectious risk Promotes GI integrity Stimulates enteric secretions, hormones and blood flow Decreased bacterial translocation

72. Enteral: Critically ill pediatric patients have multiple factors that decrease gastric emptying: Formula osmolarity Fat content Lipid carbon chain length Medications (narcotics, benzodiazepines, sedatives) Continuous feeds are best Small bowel feeds very successful

74. Causes of Diarrhea in Enterally Fed Children

75. Feeding the Hypotensive Patient Splancnic bed gets: 25% cardiac output at rest 30% of oxygen consumption is in the splancnic bed small intestine 44% * Arterial blood flow stomach 12% colon 17%

76. Feeding the Hypotensive Patient Villus tips suffer most damage during hypoxia they have the greatest digestive function. When we feed the gut, the selection of nutrients will alter the metabolic function and oxygen demand of the enterocyte.

77. Feeding the Hypotensive Patient There is the potential to do harm as the presence of food in the intestine may increase oxygen demand beyond available delivery of blood flow, leading to necrotic bowel.

78. Parenteral Metabolic Complications: Amino acids – toxic Carbohydrate – Hepatic stenosis – Cholestasis -  alk phos -  GGT -  bili Fat – depressed immune function – Reduced bacterial clearance – Increased triglycerides

79. Total Parenteral Nutrition central vs peripheral line 1000 vs 2000 mosmols/L ++ electrolyte increases osmolarity severe fluid restrictions 15+ % protein, 45% carbohydrate, 40% fat (8-10 mg/kg/min

80. Biochemistries in PICU Serum albumin, urea, triglycerides, magnesium – ↓ Mg – 20% – ↑ trig – 25% – ↑ urea – 30% – ↓ albumin – 52% ↑ uremia → ↓ SD scores for weight and arm circumference between admission and discharge ↑ triglycerides → > ventilator dependence days and length of stay than children with triglyceride levels Journal of Nutritional Biochemistry 17 (2006) 57-62

81. Nutrition Support in the ICU is not generic but: 1.Patient specific 2.Disease specific 3.Macro and Micronutrient specific 4.Biochemically specific 5.Stage specific

82. Nutritional Support of the VLBW Infant

83. Gold Standard of Growth for VLBW Infants To approximate the in utero growth of a normal fetus of the same post-conceptional age. – Body weight – Body composition

84. Unique Nutritional Aspects of the VLBW Infant Higher organ:muscle mass ratio Higher rate of protein synthesis and turnover Greater oxygen consumption during growth Higher energy cost due to transepidermal water loss Higher rate of fat deposition Prone to hyperglycemia Higher total body water content

85. Preventing Feeding-Related Morbidities in VLBW Infants Necrotizing enterocolitis Osteoporosis Vitamin and mineral deficiencies Feeding intolerance Prolonged TPN and related cholestasis Prolonged hospitalization Lack of full physical and intellectual potential

86. Optimizing Long Term Outcome Nutritional Programming: Nutrition during critical periods in early life may permanently affect the structure and/or function of organs or tissues. Alan Lucas, 1990

87. Nutritional Care/Outcomes in VLBW Infants - Potential Improvements Human milk “Early” TPN – Prevent protein deficit – Prevent EFA deficiency GI priming/MEN/Trophic feeds – Prevent GI atrophy effects – Faster realization of full enteral feeds Fortification/Supplementation – Starting earlier – Continuing longer

88. Benefits of Human Milk - Reduced Infections Otitis media – with a reduction in the frequency and duration of ear infections in breastmilk versus formula fed newborns Respiratory tract illnesses including respiratory synctial virus infection Gastrointestinal illness Urinary tract infections Infant botulism

89. GI Benefits of Human Milk for the Preterm Infant Gastrointestinal development – Reduces intestinal permeability faster – Induces lactase activity – Multiple factors to stimulate growth, motility and maturation of the intestine – Human milk empties from the stomach faster than artificial milks – Less residuals and faster realization of full enteral feedings

90. Benefits of Human Milk for the VLBW Infant Special nutritional needs – Different quantity and quality of proteins – Fats: Cholesterol, DHA, ARA – Carbohydrates designed for human infants – Lower osmolality/renal solute load – Other factors: e.g. erythropoietin, EGF

91. Parenteral Nutrition for VLBW Infants

92. Best Practice Parenteral nutrition, including protein and lipids, should be started within the first 24 hours of life. Parenteral nutrition should be increased rapidly so infants receive adequate amino acids (3.0-4.0 gm/kg/day) and calories (85- 110 kcal/kg/day) as quickly as possible.

93. Best Practice Start parenteral lipids within the first 24 hours of life. Lipids can be started at doses as high as 2 g/kg/d. Lipids can be increased to doses as high as 3.0-3.5 g/kg/day over the first few days of life.

94. Establishing Enteral Feedings

95. Best Practice Human milk should be used whenever possible as the enteral feeding of choice for VLBW infants.

96. Best Practice Enteral feeds, in the form of trophic or minimal enteral feeds (also called GI priming), should be initiated within 1-2 days after birth, except when there are clear contraindications such as a congenital anomaly precluding feeding (e.g. omphalocele or gastroschisis), or evidence of GI dysfunction associated with hypoxic-ischemic compromise.

97. Best Practice – Pumps delivering breastmilk should be oriented so that the syringe is vertically upright, and the tubing (smallest caliber and shortest possible) should be positioned and cleared to prevent sequestration of fat. – Enteral feeds should be advanced until they are providing adequate nutrition to sustain optimal growth (2% of body weight/day). For infants fed human milk this could mean as much as 170 - 200+ mL/kg/day.

98. Best Practice VLBW infants fed human milk should be supplemented with protein, calcium, phosphorus and micronutrients. Multinutrient fortifiers may be the most efficient way to do this when feeding human milk. Formula fed infants may also require specific caloric and micronutrient supplementation.

99. Human Milk and Breastfeeding

100. Transition to Oral Feedings

101. Early attachment is beneficial for milk production and mother-child bonding. Skin-to skin contact may strengthen the mother-infant dyad and lead to longer breastfeeding periods over the first two years of life. Non-nutritive breastfeeding can stimulate milk volume and improve breastfeeding success rates.

102. Best Practice Infants should be transitioned from gavage to oral feedings when physiologically capable, not based on arbitrary weight or gestational age criteria.