Parenteral Nutrition for Neonates

Parenteral Nutrition for Neonates

Definition:

• Parenteral nutrition (PN): is the intravenous infusion of all nutrients necessary to promote nitrogen retention and protein sparing, to provide energy for metabolic processes, and to establish growth and maturation during the critical postnatal period.
• Extremely Low Birth Weight (ELBW): infants with body weight < 1 kg.
• Very Low Birth Weight (VLBW): infants with body weight (1 kg – 1.5 kg).
• Low Birth Weight (LBW): infants with body weight < 2.5 kg.
• Hyperglycemia in neonates: is a blood glucose concentration > 150 mg/dl.

Background statement: Parenteral Nutrition for Neonates

• Premature infants tolerate PN from day 1 of post-natal life.
• Stable premature and term newborns generally require > 105 kcal/kg/day.
  ELBW infants require at least 75 kcal/kg/day whilst VLBW infants require at least 60 kcal/kg/day.
• Infants receiving only intravenous glucose may lose protein stores at a rate of up to 1 gm/kg/day. 2-3.5 gm/kg/day of amino acids are required in ELBW infants to support growth and nitrogen retention at a rate comparable with the intrauterine rate.
• Prompt introduction of amino-acids via the PN, decrease the frequency and severity of neonatal hyperglycemia by stimulating endogenous insulin secretion and stimulating growth by enhancing the secretion insulin-like growth factors.
• In the ELBW a minimum supply rate of glucose is 9 gm/kg/day is required to maintain adequate energy for the brain, and an additional 3-4 gm/kg of glucose per gram of protein intake are necessary to support protein deposition.
• Glucose administration is often limited by development of hyperglycemia that is attributed to peripheral and hepatic insulin resistance presumably due to glucagon, catecholamine and cortisol release and decreased insulin secretion.
• Normoglycemia is a fasting blood glucose range of 60-125 mg/dl.
• Lipids intake as little as (0.5-1 gm/kg/day) is needed to prevent essential fatty acid (EFA) deficiency, and serve as energy substrate. EFA deficiency can develop within 72 hours if exogenous fat is not administered.
• A number of clinical conditions inhibit lipid clearance. Smaller doses of lipid are used in patients with acute infection, compromised pulmonary function or hyperbilirubinemia.
• Activation of enzymes responsible for lipid clearance can be induced with the administration of low-dose heparin.
• Calcium to phosphorous molar ration below (1:1) was shown to be associated with neonatal osteopenia.
• Acetate is used to obviate acidosis since it will be converted in the blood to bicarbonate. It is shown to decrease hypercalciuria in neonates when added to TPN.

Stratification of the Aim: Parenteral Nutrition for Neonates

Indication for TPN

Generally, PN is indicated when full enteral feeding is either contraindicated or unlikely to be achieved by day 3 of age.

1. Neonates having (ELBW), (VLBW) or (LBW) even in the absence of gastric, cardiac or pulmonary disorders.
   • Necrotizing Enterocolitis.
   • GIT anomalies (omphalocele, gastroschisis, Tracheo-esophageal fistula, malrotation with volvulus, etc.).
   • Malabsorption.
   • Respiratory distress syndrome (RDS).
   • Prematurity (less than 30 weeks gestation).
   • Inadequate weight gain or a significant decrease in the usual growth percentile.

*Conditions not mentioned, may be covered if the attending physician submits an adequate documentation of the medical necessity of the service, and patient assessment determines that the service are appropriate for the condition.

Components of Intravenous Nutrition Solutions:

1. Starter solution: is used from birth, in infants with birth weight ≤ 1500 gm who don’t have central venous access. It ensures their nutritional needs are met as infusion are added or the infant is on restricted fluid intakes;
   1. In the first 2 days, the minimal allowable amount is 50 ml/kg/day. This will provide 2 gm/kg/day of protein.
   1. The usual maximal amount is 90 ml/kg/day (3.75 ml/kg/hour). It provides 3.5 gm/kg/day of protein.

Starter Solution for use from days 0-3	Usual intake at 50 ml/kg/day (2.1 ml/kg/hr)	Usual intake at 80 ml/kg/day (3.3 ml/kg/hr)	Usual intake at 90ml/kg/day (3.8 ml/kg/hr)	Usual intake at 100 ml/kg/day (4.2 ml/kg/hr)
Protein	2 gm/kg/day	3.2 gm/kg/day	3.6 gm/kg/day	4 gm/kg/day
Glucose	5 gm/kg/day	8 gm/kg/day	9 gm/kg/day	10 gm/kg/day
Calcium	0.5 mmol/kg/day	0.8 mmol/kg/day	0.9 mmol/kg/day	1 mmol/kg/day

• In preterm infants, combined PN and oral protein intakes should be limited to 4.5 gm/kg/day, in term infants; it should be limited to 4 gm/kg/day.
• As oral feeds increase protein intakes to these levels, PN will be titrated down. If medications are required (for example, inotropes), the dextrose infusion are initially decreased.

2. Individualized Total Parenteral Nutrition:
   • Fluid: fluids are usually started at 80-100 ml/kg/day (if newborn), or at whatever stable fluid intake the baby is already receiving, with the aim of delivering 150 ml/kg/day at day 7. Fluid intake decided according to gestational age, post-natal age, incubator condition and phototherapy.

Neonate (0-30 day)	Fluid volume in ml/kg/day
	Day of life
	Day 1	Day 2	Day 3 to 1 month
Wt. < 1200 gm	80-100	100-120	120-140
1200-2500 gm	70-90	80-100	100-120
2501-4500 gm	50-60	60-80	100

*Additional 10% of maintenance fluid requirements for each degree of fever above 37◦c.

• Amino acids (primene® 10%):
  • Energy value: 4 kcal/gm protein, (1 gm nitrogen = 6.25 gm protein).
  • Protein: is usually started at 1 gm/kg/day of amino acids and subsequently advanced, by 3^rd to 4^th postnatal day, to 3 gm/kg/day of protein in term and 3.5 to 4 gm/kg/day in the (ELBW) infants with normal renal/liver function.
  • Reduction in dosage may be needed in critically ill, significant hypoxemia, suspected or proven infection and high dose steroids.
  • Maximum recommended allowable concentration of amino acids solutions for infants and children is 2.5% when given peripherally and 3% when given centrally.
• Dextrose:
  • Energy value: 3.4 kcal/gm.
  • Initiation:
    • In neonates receiving IV fluids (dextrose), without experiencing hyperglycemia episodes; TPN dextrose infusion should be started at the same dextrose load provided by the current IV fluids.
    • In neonates developing hyperglycemia on current IV fluids, TPN dextrose infusion should be decreased more than the load provided by the IV fluids to be started at 6 gm/kg/day (and not < 4 gm/kg/day).
  • Advancing:
    • The advance in dextrose dosage after initiation should be gradual (1-4 gm/kg/day) as tolerated, to allow appropriate response of endogenous insulin, till the maximum recommended glucose oxidation rate (18 gm/kg/day), provided that the concentration of Dextrose in the TPN fluid will not exceed 12.5% in case of peripheral vein administration.
    • Dextrose intake above 18 gm/kg/day, tend to induce net lipogenesis that should be avoided.
    • If hyperglycemia develops; glucose infusion should be decreased, and if it still occurs at 4 gm/kg/day, insulin should be starts.
• Lipid (lipofundin 20%):
  • Energy value: 10 kcal/ml.
    • Lipid intake will be started no earlier than on day 3 of life.
    • Lipid intake will be started at (0.5-1 gm/kg/day) and gradually increased by (0.5 gm/kg/day) every 24 hours to 3 gm/kg/day (sometimes up to 3.5 gm/kg/day in the ELBW).
    • Lipid intake should provide 25-40% of non-protein calories in fully parenterally fed infants.
    • Lipid should be infused continuously over as much of the 20 hour period as practical. Lipid infusions may be administered safely to most infants at infusion rates ≤ 0.2 gm/kg/hour (1 ml/kg/hr of lipofundin 20%).
    •  Maximal plasma triglyceride (TG) concentration 200 mg/dl. Reduction of lipid dosage recommended if TG levels exceed 150 mg/dl.
  • Cautionary Use: TG should be monitored in the following cases, and accordingly a reduction of lipid dosage or a transient interruption of IV lipid supply may be considered till clinical condition improves:
    • Worsening acute lung disease: (hold lipid at 0.5-1 gm/kg/day).
    • Progressive hyperbilirubinemia (unconjugated): hold lipid dosage at ≤ 2 gm/kg/day.
    • Acute sepsis: lipid dosage may be decreased for the first 24-48 hours.
    • Unexplained thrombocytopenia.

Electrolytes	Neonatal dosage	Normal level in infants	Possible panic range
Potassium	2-3 mmol/kg/d	< 1 kg: 3.5-6.4 mmol/L 1-1.5 kg: up to 6 mmol/L 1.5-2 kg: up to 5.4 mmol/L 2-2.5 kg: up to 5	< 2.5 and > 7 mmol/L
Magnesium	0.15-0.25 mmol/kg/d	1.5-2.3 mg/dL	< 1.2 and > 4.9 mg/dL
Phosphate	0.5-2 mmol/kg/d	4.5-7.5 mg/dL	< 1.5 mg/dL
Sodium	2-4 mmol/kg/d	0-7 days: 133-146 mmol/L 7-31 days: 134-144 1-6 months: 134-142	< 125 mmol/L > 150 mmol/L
Calcium	0.25-1.5 mmol/kg/d	Premature: 6.2-11 mg/dL 0-10 days: 7.6-10.4 mg/dL 10 days-24 mo: 9-11 mg/dL	< 7 mg/dL and > 12 mg/dL
Chloride	2-4 mmol/kg/d	Premature: 95-110 mmol/L Full term: 96-106	< 80 and > 115 mmol/L
Acetate

• Electrolytes:
  • Maximum dose of 1.5 mmol of calcium and phosphorous per 100 ml of PN solution can only be attained if the total amino acid concentration is 3%.
    • Sodium will be started either as sodium acetate or as combination of sodium acetate and sodium chloride to maintain acetate approximately equal or slightly less than chloride load in TPN solution.
    • If acidosis develops, decrease chloride and increase acetate, while if alkalosis; decrease acetate and increase chloride load in TPN (normal PH of blood: 7.35-7.45, panic range < 7.2 and > 7.55) (PHCO3: 16-24 mmol/L; panic range < 10 & > 40 mmol/L).
      • False high results of potassium, magnesium, calcium and phosphorous should be considered in hemolyzed samples.

• Vitamins: dosage will be determined based on available product Cernivit® is an intravenous multivitamin combination of both water and fat-soluble vitamins presented in one vial. Vitamin K1 (phytonadione) and is not provided in the Cernivit®.

Wt. (kg)	Dosage (ml)
< 1 kg	1.5 ml
1-3 kg	3 ml
> 3 kg and up to 11 years of age	5 ml

Vitamin	Each 5 ml cernivit contains:
Vitamin A	3500 IU
Thiamine	5.80 mg
Riboflavin	5.67 mg
Pyridoxine	5.50 mg
Vitamin B12	6 mcg
Biotin	69 mcg
Folic acid	414 mcg
Niacinamide	46 mg
Dexapanthenol	16.15 mg
Vitamin C	125 mg
Vitamin E	10.2 mg
Vitamin D	220 IU

• Trace elements: Dosage to be determined by pharmacy based on the available product:

Trace elements	Infants and toddlers mcg/kg/day
Copper	20
Zinc	Premature: 300 < 3 months old: 150 > 3 months old: 100
Manganese	1
Chromium	0.2
Selenium	2
Molybdenum	0.25
Iodide	1

• Pediatric trace elements:
  • Pediatric trace elements shall be used for neonatal and pediatric patients.
  • If the daily requirements of zinc, was not fully provided by the determined dosage of trace elements, an additional amount of zinc, will be added to TPN.
  • Caution in case of impaired renal or liver functions. Trace elements should be discontinued in liver impairment and only zinc and selenium should be provided. Selenium is contraindicated in renal impairment.
  • Iron content of the used product of trace elements should be checked, for possible replacement with iron supplement when needed. Iron: 0.1-0.2 mg/kg (initiate at 6 weeks of age for infants on TPN if ferritin < 500 ng/ml).
  • Normal ferritin: (newborns: 25-200 ng/ml, 1 month: 200-600 ng/ml, 2-5 month: 50-200 ng/ml, 6 m- 15 years of age: 7-140 ng/ml).

• Heparin:
  • 0.5 unit of heparin may be added to each 1 ml of the TPN solution particularly for central venous administration to maintain patency of the line; provided that there is no contraindication.
  • Heparin administration should be considered in infants younger than 26 weeks gestation and in ELBW infants who demonstrate lipid intolerance, even those receiving TPN via peripheral vein.

• Insulin:
  • Insulin in D10%W will be infused at 0.01-0.1 unit/kg/hour, in infants with blood glucose level > 200 mg/dl. The infusion rate then is adjusted based on frequent measurements of plasma glucose concentration to achieve and maintain concentrations between 80 and 120 mg/dL.
  • Insulin will not be added to the PN solution.

• Carnitine: Carnitine supplementation may be considered on an individual basis in infants receiving Carnitine free-TPN for more than one month.

Administration Parenteral Nutrition for Neonates

when administered peripherally, the maximum osmolarity in Neonates and Infants MUST NOT exceed 1100 mOsmol/L.

Monitoring Parenteral Nutrition for Neonates

Recommended Frequency for Routine Monitoring Parameters

Routine Monitoring Parameters	Recommended Frequency
Urinary; glucose, ketones and specific gravity	Every voided specimen until stable, then daily
Finger stick glucose	Every 6 hours until stable
Temperature, Vital signs	Every 4 hours
Body weight, fluid intake and output	Daily
Serum; glucose, Na, K, CL, HCO3, osmolarity, creatinine, and BUN	Daily until stable, then twice weekly
Magnesium, Calcium and Phosphorous	Daily until stable, then once weekly
CBC, and prothrombin time. INR	Baseline then weekly
Serum protein, albumin	Baseline then weekly
Prealbumin (when BUN & Albumin are low)	Baseline then weekly
Liver function tests	Baseline then twice weekly
Serum cholesterol and triglycerides	Every day for 2 days then weekly
Blood ammonia	Baseline then weekly in renal and hepatic pt.

For preterm and term neonates, the risk of frequent blood sampling should be weighed against the potential benefits of the information obtained from these laboratory tests, as the frequent withdrawal of blood for monitoring electrolytes and other parameters may rapidly deplete the neonate’s blood supply due to neonates have a relatively small blood volume.

Discontinuation of TPN – Parenteral Nutrition for Neonates

TPN should be discontinued when an infant is tolerating 75% of full enteral feeds. If TPN be in hold, with no oral feeding commenced; dextrose solution (5% or 10%) should be infused at the same rate the TPN was infused to avoid rebound hypoglycemia.

References

1. Guidelines on Peadiatric Parenteral Nutrition of the ESPGHAN and the ESPEN, J Pediatr Gastroenterol Nutr 2005; 41 Suppl 2:S1-87.
2. Osteopenia in Neonates: A Review, www.hkipaed.org/pdf/2007.
3. American Journal of Clinical Nutrition, Vol 48, 1482-1489, Copyright © 1988 by The American Society for Clinical Nutrition, Inc Acetate and hypercalciuria during total parenteral nutrition.
4. Lipids; Journal of Pediatric Gastroenterology and Nutrition, November 2005.
5. 1999 American Academy of Pediatrics Early Aggressive Nutrition in the Neonate.
6. McMaster Children’s Hospital, NICU Nutrition Guidelines.
7. Laboratory Test Handbook 3^rd Edition (2001).