1. Dr.f.razmpour .MD.PhD candidate of clinical nutrition
TPN in neonate
Dr.f.razmpour .MD.PhD candidate of clinical nutrition

2. Newborn Classifications-Definitions:
LBW: Low Birth Weight
<2500g
VLBW: Very Low Birth Weight
<1500g
ELBW: Extremely Low Birth Weight
<1000g
Preterm: <37 weeks GA
Late Preterm: 34 – 36 weeks GA

3. 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
Goals of Nutrition

4. Gastrointestinal Development
Fetal swallowing, motility in 2nd trimester
18 week fetus swallows 18-50ml/kg/day
Term ml/day
Fetal swallowing regulates the volume of amniotic fluid and controls somatic growth of the GI tract
Intestines double in length from weeks
Functionally mature gut by 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
Gastrointestinal Development

5. Typical Feeding Progression
Gestational Age (Weeks)
Pacifier Sucking (non-nutritive suck)
Gag Reflex
Rooting Reflex Early Intermediate Mature
Coordinate Suck,
Nutritive Suck Swallow, Breathe
TPN for 1-2 weeks as enteral Gradually start breast/ Infant nippling
feeds advance via tube bottle per infant cues all feeds

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

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

8. Postnatal Growth Failure
Growth failure in preterm:
-Higher nutrient requirements
- Endocrine abnormalities
-Central nervous system damage
Difficulties in suck and swallow coordination
Administration of drugs that affect nutrient metabolism.

9. Fetal Nutrition
In utero, the transfer of glucose across the placenta averages 8 mg/kg/min in the third trimester.
Amino acids…..
Lipids……

10. 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
Growth – General Facts

11. 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
Fetal nutrition

12. Early Parenteral Nutrition
The sudden change from the well-fed state in utero to the extra-uterine environment challenges the preterm infant.
A preterm infant of 1 kg consists of only 1% fat and 8% protein and has a non-protein caloric reserve of 110 kcal/kg body weight.
When preterm infants do not receive exogenous substrates after birth, either enteral or parenteral, the infant reaches a catabolic state immediately.
When receiving only glucose after birth, the estimated protein loss is approximately 1% of the endogenous body protein per day.

13. Monitoring for feed intolerance
Indicators:
Infants < 1000g: >2ml gastric aspirates every four hours (10- 20ml/kg/day)
Infants > 1000g: >3ml gastric aspirates every four hours (15- 20ml/kg/day)
Other indicators:
vomiting
abdominal distension
abdominal discolouration
blood per rectum
increase in stool frequency

14. Increase caloric requirements

15. Fluids
Fluid tolerance is limited in the first days of life due to renal adjustment but there is large variability among very low birth weight infants.
Commonly fluid intake is increased daily in the first week of life. Fluid volumes between 80 and 200 ml/kg/day are tolerated well and these values may serve as lower and upper limits. A postnatal intake at the lower end of the range is likely to minimise risk of long-term morbidity such as brochopulmonary dysplasia and patent ductus arteriosus.
Current guidelines recommend 135 ml/kg/day as the minimum fluid volume and 200 ml/kg/day as a reasonable upper limit, to be reached after several days.

16. Fluid

17. Carbohydrates
In premature infants, the endogenous glucose production is not adequate to provide the demands and, there are few alternative fuels. Therefore, premature infants are dependent on parenteral glucose administration.
Furthermore, the insulin response to hyperglycaemia is limited in VLBW and, especially in SGA babies, insulin resistance is more pronounced.
Lipid emulsions may however help to stabilise glycaemia as glycerol is a substrate for gluconeogenesis.

18. Carbohydrates
Current guidelines suggest starting with a glucose infusion at 6 mg/kg/min directly after birth, with a daily increase rate of 1-2 mg/kg/min, or more if hypoglycaemia (<50 mg/dl) occurs.
Generally the maximal glucose intake is 12 mg/kg/min.
If blood glucose exceeds 180mg/dl glucose administration can be decreased by 2 mg/kg/min but not below 6 mg/kg/min. Consider insulin infusion at a rate of IU/kg/hr depending on the blood glucose level and increase insulin up to 0.2 IU/kg/hr to keep the blood glucose at mg/dL.

19. Proteins/Amino Acids
, due to immaturity of different enzyme systems, premature infants are not able to synthesize an additional 4 amino acids, namely arginine, glycine, proline and tyrosine (conditionally essential amino acids).

20. What time should be start using amino acids?
Early amino acid delivery may improve glucose tolerance by enhancing endogenous insulin secretion.
IGF-1 is lower in premature infant and may further reduced by inadequate protein intake.
Low level of IGF-1 are associated with increased risk of ROP,BPD,IVH and NEC

21. Proteins/Amino Acids
Current guidelines recommend starting amino acid supply on the first postnatal day, with an amount of 2.4 g/kg/day.
A further increase to
g/kg/day for infants up to 1000g
3.5 – 4.0 g for infants from 1000 to 1800 g is recommended.
The amino acid intake can be reduced towards discharge if the infant’s growth pattern allows for this

22. Lipids
Brain grey matter and the retina are particularly rich in LCPUFA, and complex neural functions are related to energy supply and the composition of dietary fatty acids. Parenteral lipid emulsions are an attractive source of nutrition, because of their high energy density (9 kcal/g) – compared to glucose (4 kcal/g).
The high energy density is furthermore useful since fluid restriction is commonly necessary in preterm infants.

23. Lipids
A major concern during administration of parenteral lipids is the development of parenteral nutrition associated liver disease (PNALD). PNALD symptoms:
mild cholestasis to end stage liver disease requiring liver transplantation.
The prevalence of PNALD in infants differs widely, ranging from 15-
85%.
The most significant risk factor is prematurity. This may be due to the reduced bile acid pool size and immature entero hepatic circulation in preterm infants.
Furthermore, preterm infants are more likely to be in need of long term PN.

24. Recommendation
The current recommendation is to start intravenous lipid administration not later than on the third day of life, but it may be started on the first day.
The maximum dose of parenteral lipid administration is 3-4 g/kg/day, which dose can be reached within 3 days from starting.
In order to prevent essential fatty acid deficiency, g/kg per day linoleic acid (ALA) should be included.

25. 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
Total Parenteral Nutrition

26. Complication Hyperlipidemia
Potential risk of kernicterus at low levels of unconjugated bilirubin because of displacement of bilirubin from albumin binding sites by free fatty acids.
As a general rule, do not advance lipids beyond 0.5 g/kg/d until bilirubin is below threshold for phototherapy
Potential increased risk or exacerbation of chronic lung disease
Potential exacerbation of Persistent Pulmonary Hypertension (PPHN)
Lipid overload syndrome with coagulopathy and liver failure

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

29. Early Enteral Nutrition Trophic or Minimal-enteral Feeding
Immature the gastro-intestinal tract:
both morphologically and functionally.
Motility is sparse
barrier function is incomplete
immunological defence is immature
Due to the hospital environment and antibiotic use, the prevailing microbiota are abnormal. All of these factors predispose to NEC.
Because gut hormone secretion and motility are stimulated by ingesting milk, delayed enteral feeding could diminish functional adaption of the gastrointestinal tract, and result in later feeding intolerance.
Lack of enteral nutrition causes gut atrophy, with an increased risk of bacterial translocation.

30. Minimal Enteral Feeding
enhanced activity of digestive enzymes
increased digestive hormone levels
improved gut motility compared to infants not receiving MEF
tolerated well in preterm infants
associated with earlier achievement of full enteral feeding
decreased duration of parenteral feeding
decreased length of hospital stay
without an increase in the incidence of NEC.
MEF can be defined as the administration of very small amounts of enteral feeding, which may be less than 25 ml per day to infants who are still dependent on parenteral feeding.

31. guidelines
Current guidelines recommend starting MEF on the day of birth in infants who are not able to receive normal enteral feeding.
There is a strong preference for milk from
the child's mother, 12 to 25 ml each day, to be divided into portions.
If MEF is well tolerated enteral feeding can be increased.

32. Choice of Milk
Current guidelines recommend adding breast milk fortifier to meet the infant's nutritional requirements; this contains extra protein, energy, vitamins and minerals.
Fortifiers contain approximately 0.8 g of protein per 100 ml of milk.
Fortification can be started when 100 ml/kg of enteral feeding is tolerated.

33. Human milk shortcomings if preterm
Human milk may not provide enough
Protein
Energy
Sodium
Calcium, phosphorus and magnesium
Trace elements (Fe, Cu, Zn)
Vitamins (B2,B6,Folic acid, C,D,E,K)
Human milk shortcomings if preterm

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

35. 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
Term vs preterm formulas

36. 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
Feeding preterm infants: aim

37. Growth Assessment Start with correct growth parameters
Term-
3 mo CA
3-6 mo CA
Weight Gain
~6-8 oz/wk
~4 oz/wk
Length Gain
~1 cm/wk
~0.5 cm/wk
HC Gain
~0.2 cm/wk

38. Corrected Age
Use corrected age for all premature infants <37 weeks until 24 months when assessing:
Growth
Nutritional needs
Feeding (solids, cow’s milk)
Developmental milestones

39. Parenteral Nutrition for VLBW Infants

40. 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 ( gm/kg/day) and calories ( kcal/kg/day) as quickly as possible.
Best Practice

41. Start parenteral lipids within the first 24 hours of life
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 g/kg/day over the first few days of life.
Best Practice

42. 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.
Best Practice

43. Parenteral in term neonatal

44. 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
Parenteral Nutrition

45. Energy Requirements kcal/kg/day Basal metabolic rate 40
Physical activity 4+
Specific dynamic action of food (10%)
Thermoregulation variable
Growth
(To match in-utero growth of 15g/kg/day)
Energy

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

47. 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
Caloric Requirements for Growth

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

49. 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
Monitor: renal function, albumin
Protein

50. 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)
maximum 60% of total energy
Fat

51. Evidence Based Nutrition
RA Ehrenkranz, Seminars in Perinatology 2007 (31): 48-55
1394
norozy dr

52. 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 ) ÷ 12 = 10.3mg/kg/min
(15% x 8.3 ) ÷ (6 x 2) = 10.3 mg/kg/min
Total Parenteral Nutrition

53. 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
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 = mg/kg/day (NOTE: mg not mEq and Ca cannot be infused at >200mg/kg/day through a peripheral line)
Total Parenteral Nutrition

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

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

56. Total Parenteral Nutrition
Central TPN
Peripheral 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
Total Parenteral Nutrition

57. 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
Developmental Origins theory

58. 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
Laboratory assessment

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

60. Question…