Neonatal TPN guidelines

[Russell Carter]

I need neonatal TPN guidelines specially daily requirements for starter and regular formula

If any one have a valid resource and reference for this specific population ,please share it

[Naveed Rivas]

Download the file as pdf in the link below..

https://mega.nz/file/r84jBSIK#IxdMpVWgQoprqgofHHf1AfuLQVsSoHWC8Yvod6vheig

Also I’ve copied the text for you. if you want a faster source.

Hope this helps.

Introduction

PN has the potential to maintain nutritional intake until the establishment of enteral  feeds in preterm infants and in more mature infants with significant gastrointestinal  malformation  or  malfunction  which  precludes  milk  feeding.  PN  may  be  the  only  source  of  nutrition,  or  supplied  in  conjunction  with  milk  until  tolerance  of  sufficient  enteral nutrition has been achieved.     

There is currently much variation within the UK in the provision of neonatal PN with  regard to its use and availability as well as its constituents. The National Confidential  Enquiry into Patient Outcome and Death (NCEPOD) enquiry into the care of hospital  patients receiving PN in 2008 analysed data from 264 neonates in England, Wales  and  Northern  Ireland.  Only  23.5%  had  received  PN  care  considered  to  represent  good practice (1). 12 babies (4.5%) received less than satisfactory care, and room for  improvement was identified in clinical care (40.5%), organisational care (9.5%) and in  both clinical and organisational care (18.6%) in a majority, figures broadly similar to  adult  practice.  A  subsequent  report  from  the  Paediatric  Chief  Pharmacist’s  Group  (PCPG)  endorsed  concerns  in  the  NCEPOD  report  regarding  issues  in  prescribing  and  administration  of  neonatal  PN,  and  highlighted  variation  in  practice  between  units,  particularly  for  ELBW  babies  (2).  The  PCPG  defined  minimum  standards required to deliver PN in the NHS setting and recommended seeking consensus in  best PN neonatal practice.  

The ELBW infant has sufficient energy reserves to support only the first 2 – 3 days of  life and even well grown term infants will rapidly become catabolic if not supplied with  adequate  protein  and  calories.  All  significantly  preterm  infants  are  at  risk  of  early  postnatal growth failure coinciding with the development of a cumulative nutritional  deficit and linked to poorer neurodevelopmental outcome (3). Optimising growth and  nutrition  in  the  early  weeks  of  life  results  in  improved  head  and  somatic  growth  although studies of longer-term neurocognitive outcome are lacking (4,5). 

The primary purpose of neonatal PN is to achieve adequate (or as near adequate as  possible) nutrition, thus permitting appropriate growth. In the absence of evidence to  define appropriate growth for preterm infants, we suggest using in-utero growth as  the reference. It is not clear if, when or at what rate any early postnatal fall in weight  centile should be regained (6). 

Administration of neonatal PN is necessarily linked with fluid balance, particularly in  the  first  few  days  of  life,  but  the  nutritional  needs  of  the  neonate  should  be  considered  independently  of  fluid  requirements.  A  good  understanding  of  normal  neonatal physiology is essential for those involved in prescription and administration  of PN.  

PN is expensive and carries significant risks including toxicity, metabolic disturbance  and  line-associated  sepsis.  All  neonatal  units  using  PN  should  undertake  regular  audit of practice, including attainment of target nutritional intake.    

Who should receive PN, and when?

No study has defined the ideal criteria for administration of neonatal PN, so clinical  judgement  needs  to  be  applied  in  balancing  benefits  and  risks,  which  will  vary  according  to  postnatal  and  gestational  age.  We  recommend  that  PN  be  routinely  available  for  infants  born  before  30  completed  weeks’  gestation  (i.e.  up  to  and  including 29 weeks and 6 days), and for all infants weighing < 1250 g at birth (Table  1). Additionally, PN should normally be provided for any infant, term or preterm who  has  failed  to  establish  enteral  nutrition  (as  defined  by  a  feed  volume  of  >  100  mL/kg/day) by day 5 of life or who subsequently fails to tolerate enteral nutrition over  a  significant  period.  Infants  of  any  gestation  who  are  not  predicted  to  establish  enteral nutrition by day 5 should also be considered for PN. All services caring for neonates meeting these criteria should have 24-hour access to PN, 7 days a week.  

Table 1: Indications for PN in neonates

Absolute Indications

Gestational  age  <  30  completed  weeks  (i.e.  up  to  and including 29 weeks and 6 days) Birth weight  < 1250 g   Failure  to  establish  enteral  nutrition*  by  day  5  of  life, regardless of gestation or birth weight Inability to tolerate enteral nutrition for a period likely to result in a significant nutritional deficit**  *Enteral nutrition defined as > 100mL/kg/day milk **The likelihood of a significant nutritional deficit depends on many  factors  including  age,  gestation,  and  birth  weight.  PN should  be  considered  for  any  baby  >  5  days  of  age  who becomes unable to tolerate enteral feeds for > 24 hours

Relative Indication

Any  baby  >  30  weeks  gestation  considered  unlikely  to establish enteral nutrition by day 5.

The duration of PN, as well as the period of intolerance of enteral feeding considered  significant will be determined by gestation, birth weight and other morbidities as well  as local preferences for advancement of enteral feeds. In some cases secure venous  access may also be a consideration. Local nutrition guidelines should be agreed and  implemented, as this helps to achieve consistency of practice and shortens time to  full enteral feeds (7). It is important that nutrition guidelines are regularly reviewed as  the results of feeding trials become available.      

Newborn  infants  meeting  an  absolute  criterion  for  PN  should  be  started  on  intravenous (IV) glucose and amino acid (AA) solution as soon after birth as possible  and  IV  lipid  added  within  24  hours.  Normally  PN  will  be  commenced  immediately  after  a  central  venous  line  has  been  sited  and  its  position  deemed  acceptable  although PN may be administered peripherally (see below). Similarly, there should be  no delay in commencing PN in older, more mature babies once a decision for PN has  been made. We strongly recommend that nutritional intake be considered separately  from fluid management, but acknowledge that for relatively stable babies a stepwise  increase in total volume of infused fluid of a constant glucose and AA solution may  be considered the most appropriate way to manage PN in the first few days of life.   

 

Constitution of PN (summarised in Table 2, appendix)

Water and electrolytes:

Although the primary purpose of neonatal PN is to achieve adequate nutrition, fluid and electrolyte balance will need to be considered, particularly in the first few days of  life when there may be rapid changes in both intracellular and extracellular body fluid  compartments.  It  is  reasonable  to  start  on  day  1  with  fluid  volumes  of  60  –  100  mL/kg/day,  increased  according  to  the  baby’s  clinical  condition.  Measured  fluid  balance  is  unreliable  and  must  be  interpreted  with  caution;  daily  weighing  of  the  smallest  and  sickest  babies  is  essential.  To  facilitate  consistency  of  nutrition,  PN  content  may  be  calculated  to  provide  daily  nutrient  requirements  in  a  minimum  acceptable fluid volume, with additional fluids and electrolytes infused separately as  required.  Such  concentrated  PN  solutions  allow  prompt  changes  in  fluid  and  electrolyte  management  without  need  for  changes  to  the  PN  solution  but  require  more complex calculation of fluid and electrolyte intake, with increased potential for  prescription  and  administration  error.  For  a  majority  of  stable  babies,  fluid  requirements are reasonably predictable and can be managed by stepwise increase  in volume of standard PN solutions, recognising that this practice is unlikely to meet  full nutritional requirements in the first week of life. 

1.  Sodium

Following the immediate postnatal physiological diuresis, at least 1 – 3 mmol/kg/day  of  sodium  should  be  provided  in  PN  from  48  –  72  hours  of  life.  Faecal  and  renal  losses  in  the  smallest  preterm  infants  may  result  in  much  higher  sodium  requirements.  Small  amounts  of  sodium  may  safely  be  given  in  the  first  two  days,  and  will  necessarily  accompany  phosphate  supplementation  of  PN  fluids.  More  evidence  is  required  to  define  sodium  requirements  for  optimal  early  nutrition.    Measuring  urinary  sodium  losses  may  help  to  guide  sodium  supplementation  after  the first few days.

2.  Potassium

Extracellular  potassium  concentration  is  affected  by  blood  pH  and  may  not  reflect  intracellular concentration. Assuming adequate urine production, 1 – 2 mmol/kg/day  potassium  should  be  commenced  from  48  –  72  hours  of  age,  increased  to  2  –  3  mmol/kg/day (or more as required) from week two. Requirements may be higher in  preterm  infants  and  will  be  affected  by  the  presence  of  renal  or  gut  pathology,  external cerebrospinal fluid drainage or diuretic therapy. Small amounts of potassium  will be present in PN fluids containing acetate salts.

3.  Chloride

The intake and output of chloride usually parallels that of sodium, but chloride losses  will be modified by bicarbonate status. Additional chloride is often infused with other electrolytes (e.g. potassium chloride); since excess chloride administration may result  in metabolic acidosis, use of acetate salts should be considered (8).    Recommendations for practice   

• Regular monitoring of water and electrolyte balance in neonates receiving PN should be undertaken. The best guide to overall fluid balance is measurement  of body weight; electrolyte balance should be considered in conjunction with  plasma electrolytes. ELBW babies will normally require 12 hourly monitoring,  at least for the first 48 – 72 hours of life.

• Only small amounts of sodium are generally required in the first 48 hours of life.

• Refinements to  fluid  and  electrolyte  balance  may  be  achieved  either  by  changes to the total prescribed volume of PN or by titration of additional fluid  and electrolyte solutions in addition to concentrated PN solutions. Whichever  method  is  practised,  nutrient  provision  should  be  considered  in  addition  to  fluid balance.

Energy:

PN must supply sufficient energy to cover energy expenditure and losses in addition  to growth. Resting energy expenditure increases over the first few weeks of life, with  significant  inter-individual  variability  (9);  in  a  relatively  stable  small  preterm  infant  towards the end of the first week resting energy expenditure will be around 80 – 95  kcal/kg/day. Fetal energy accretion is approximately 24 kcal/kg/day, so provision of  100 – 120 kcal/kg/day is recommended for neonatal PN (10). Energy requirements  are slightly less in the parenterally, compared to enterally fed infant. Since protein is  required for tissue repair and new tissue deposition, the majority of energy provision  in PN should be non-nitrogen (i.e  from carbohydrate and/or lipid). 

Recommendation for practice

• For most stable neonates PN should provide a total of 100 – 120 kcal/kg/day (including 85 – 100 non-nitrogen kcal/kg/day) by 72 hours of age.  Carbohydrate:  Glucose is the major source of energy for most metabolic processes in the body and  is  also  an  important  source  of  carbon  for  the  synthesis  of  non-essential  fatty  and  amino  acids.  D-glucose  (dextrose),  the  main  carbohydrate  and  energy  source  in  neonatal PN, provides 3.4 kcal/g. It should be noted that carbohydrate provides on  average 4 kcal/g; this latter formula is commonly used for calculation of PN content. 

Considerations

1.  Glucose production and utilisation

Term infants produce around 5 mg/kg/min glucose.  Preterm infants can produce up  to  5  mg/kg/min  glucose  from  glycogenolysis  and  a  further  4  –  5  mg/kg/min  from  gluconeogenesis.  This  production  continues  in  the  face  of  IV  infusion  of  adequate  amounts  of  glucose,  and  may  contribute  to  hyperglycaemia.  Glucose  utilisation  in  term infants is around 3.5 – 4.5 mg/kg/min but may be double this in preterm infants  (10).    

2.  Provision of glucose in PN

ESPGHAN  guidelines  advise  daily  glucose  intakes  of  5.8  –  17.3  g/kg  (4  –  12  mg/kg/min) in the neonatal period (11). PN protocols providing energy at the upper  end  of  this  recommendation  in  conjunction  with  higher  protein  are  associated  with  more  rapid  return  to  birth  weight  and  improvement  in  both  weight  gain  and  head  circumferential growth, without increase in relative body fat (5,12,13).

3.  Risks of excessive glucose intake

1. Excess fat deposition

Abnormal body composition at term equivalent age, with excess fat and a lack  of lean mass has been described in preterm infants (14). This may be due at  least  in  part  to  a  combination  of  excessive  energy  provision  and  inadequate  provision of protein, and is likely to be modifiable depending on early nutrition  strategy (15).  

1. Hyperglycaemia

Neonatal hyperglycaemia is reasonably consistently defined as a whole blood glucose  concentration  >  6.9  mmol/L  or  a  plasma  or  serum  glucose  concentration  >  8.3  mmol/L.  Hyperglycaemia  is  common  in  very  preterm  infants, but although associated with an  increased risk of mortality and many  other complications of prematurity there is no evidence of a causal relationship  (16).    

4.  Management of neonatal hyperglycaemia in association with PN 

Hyperglycaemia may be tolerated providing that no metabolic complications such as  dehydration  and  metabolic  acidosis  arise.  Treatment  options  include  glucose  reduction  and/or  insulin  therapy.  There  is  no  definitive  evidence  to  guide  practice  (16).     

1. Glucose reduction

Glucose  reduction  results  in  lower  energy  intake  with  potentially  impaired  utilisation of AA and a risk of growth failure. Lower energy intakes in the first week  of  life  are  associated  with  poorer  neurodevelopmental  outcome  (17).  Glucose provision should not be reduced below 5.8 g/kg/day (4 mg/kg/min).

1. Insulin therapy

The main risk relating to insulin therapy is hypoglycaemia; this risk is likely to be  less  if  insulin  is  used  to  treat,  rather  than  prevent  hyperglycaemia  (18).  Nutritional strategies promoting rapid early growth may have implications for the  later  development  of  metabolic  syndrome  (19)  although  there  is  currently  no  evidence  linking  the  latter  with  insulin  therapy  in  preterm  infants.  Studies  demonstrating improved neonatal growth with high protein and energy intakes  have used insulin therapy to treat hyperglycaemia (5,12,20). 

1. AA and lipid intake

AAs stimulate insulin secretion in preterm infants and early AA administration is  associated  with  a  lower  incidence  of  hyperglycaemia  (21).  Increasing  early glucose  and  AA  intake  simultaneously  does  not  increase  the  risk  of  hyperglycaemia.  There  is  some  evidence  that  IV  lipid  may  exacerbate  hyperglycaemia via stimulation of gluconeogenesis (18).

Recommendations for practice

• Regardless of  gestation,  the  minimum  amount  of  glucose  that  should  be  provided in the first 24 hours is 5.8g/kg/day.

• For both  preterm  and  term  infants,  glucose  intake  should  be  increased  as  tolerated. The maximum intake should not exceed 17.3 g/kg/day.

• A local  policy  should  be  agreed  for  the  management  of  hyperglycaemia.  When  interventions  are  deemed  necessary,  these  may  include  reduction  of  glucose  intake,  use  of  insulin,  early  AA  administration  and/or  avoidance  of  high early lipid provision. 

Protein/amino acids:

Protein is required for cell structure and function and is provided in PN in the form of  AA. PN protein is estimated from the nitrogen content of the fluid; depending on the  AA  formulation,  protein  content  will  be  up  to  12%  lower  than  the  AA  content.  Calculating PN protein intake (g/kg/day) may be useful in order to allow total (enteral  and parenteral) protein intake to be ascertained. Neonatal PN AA formulations are  designed to provide a full range of AA including the essential, conditionally essential  and  non-essential  AA  required  for  protein  synthesis,  and  to  reflect  as  closely  as  possible  umbilical  cord  blood  or  human  milk  protein  AA  profiles.  Formulations  are  limited by solubility and stability of AA; in addition, the bioavailability of some AA is  affected  by  metabolic  demands  other than  protein  synthesis  and  by  metabolism of  milk  proteins  in  the  gut  (22).  Since  the  intestine  is  bypassed  in  PN,  the  AA requirement  should  be  less  than  for  enterally  fed  babies,  but  this  may  be  partially offset by unpredictable absorption and metabolism of specific amino acids.  

Considerations

1.  Protein utilisation and accretion

The minimum protein intake required to prevent loss of existing tissue protein is 1.5  g/kg/day (11). In infants of less than 29 weeks’ gestation, starting 1.5 – 2.4 g/kg/day  parenteral protein immediately after birth achieves a positive nitrogen balance in the  first  48  hours  of  life  (23).  Increasing  parenteral  protein  intake  thereafter  up  to  3.6  g/kg/day  in  association  with  90  kcal/kg/day  of  non-protein  energy  further  improves  nitrogen retention without significant biochemical derangement other than increased  plasma  urea  concentration  (24,25). There  is  a  paucity  of  evidence  in  more mature  preterm infants and in term infants.    

2.  Provision of AA in PN

Interpretation and comparison of published studies is difficult due to variation in study  populations  and  differences  in  rates  of  incrementation  of  protein  and  calories,  energy:protein ratio and outcome measures.

1. Starting dose

Nitrogen  balance  is  not  improved  by  starting  doses  of  >  3.5  g  protein/kg/day compared to starting doses of 1.5 – 2.4 g/kg/day (24,26). 

1. Target protein and energy intakes

Protein intakes of 3.5 – 4 g/kg/day in association with non-protein energy:protein  ratios  of  21  –  25  are  associated  with  improved  growth  outcomes  (4,12,20).  Similar  protein  intakes  in  association  with  lesser  non-protein  energy:protein  ratios do not however improve nitrogen retention or lean body mass compared  to  protein  intakes  of  2.7  g/kg/day  (15,24).  The  ratio  of  energy:protein  in  PN  almost  certainly  influences  utilisation  of  AA  and  promotion  of  optimal  body  composition and although there is a paucity of evidence, it is likely that 18 – 25  non-nitrogen kcal are required per g protein (10,15).   Attainment of target protein dose may be challenging, particularly in the first two  or  three  days  and  attention  needs  to  be  paid  to  the  actual  protein  intake  achieved.  The  actual  daily  intake  should  reach  the  target  daily  intake  before  day 5 in order that the total target protein intake for the first week of life can be  met. There is evidence that using concentrated PN solutions results in better  attainment of target protein intake (20).  

1. Optimal neonatal PN AA formulation

There are no studies comparing different neonatal PN AA formulations. Current  formulations  do  not  result  in  optimal  plasma  AA  profiles,  which  may  have  implications  for  the  efficiency  of  protein  synthesis  and  carry  a  risk  of  toxicity  (27,28). Many of the AA products in current use have formulations that are 25 years  old  and  safety  data  are  largely  based  on  small  historical  preterm  populations. There is a need for new evidence.   

3.  Longer term outcomes

Observational  studies  have  associated  higher  early  protein  and  energy  intake  with  improved  neurodevelopmental  outcome  at  18  months  but  data  from  randomised  controlled  studies  are  limited.  The  SCAMP  study  showed  improved  early  head  growth with increased protein and energy intake in very preterm infants (4) but in the  similarly sized NEON study increased amino acid provision without increased energy  intake was associated with poorer head growth (15). There has been no randomised  controlled  trial  of  increased  parenteral  protein  and/or  energy  powered  to  evaluate  neurodevelopment  or  longer  term  metabolic  complications  as  a  primary  outcome  (29).   

Recommendations for practice 

• Preterm infants
• Preterm infants meeting at least one criterion for PN at birth should be started on protein as soon as possible at a dose of 2 – 2.5 g/kg/day.
• Target parenteral protein intake should be 2.7 – 4 g/kg/day by day 5 of life, regardless  of  age  at  commencing  PN  and  assuming  adequate calorie intake.
• Term and  larger  preterm  infants  (>  34  weeks’  gestation  unless  significant intrauterine growth restriction)
• Target protein intake should be 3 g/kg/day by day 5 of life.
• The choice  of  parenteral  AA  formulation  for  each  network  provider  should involve dietetic as well as pharmacy expertise.  

Lipid:

As well as fat and calories for growth, IV lipids  provide n-6 and n-3 essential fatty  acids  for  brain  development;  without  supplementation  ELBW  infants  risk  becoming  deficient  in  essential  fatty  acids  within  two  days  of  birth  (30).  IV  lipid  reduces  lipogenesis and is associated with decreased energy expenditure, reduced oxygen  consumption  and  carbon  dioxide  production  and  improved  nitrogen  retention.  20%  lipid emulsion provides  2 kcal/mL, more than five times the calorie density of 10%  glucose and AA solutions. 

Considerations

1.  Lipid utilisation and accretion

The  fetal  requirement  for  fatty  acids  increases  during  the  third  trimester  from  approximately 1.0 g/kg/day to just over 2.0 g/kg/day at term (10).

2.  Provision of lipid in PN

a. Starting dose

IV  lipid  is  generally  well  tolerated  from  birth  even  in  ELBW  babies  (31,32).  VLBW  babies given  2  g  lipid/kg/day  on  day  one  and  3  g  /kg/day  on  day  two  have improved nitrogen retention compared to VLBW babies given glucose and  AA solution alone (24). 

b. Target lipid intake 

IV lipid provision of up to 3.5 g/kg/day in the first week of life is well tolerated in  VLBW  infants  and  associated  with  improved  energy  intake  and  weight  at  hospital discharge (32).

c. Which lipid preparation to use?

Newer lipid formulations include medium chain triglycerides, olive oil and fish  oils as well as soybean oil; these may beneficial in babies with liver disease but  long term data are lacking (33). A weak association between these newer lipids  and reduction in sepsis has been described but there is no clear evidence of  benefit  or  harm  from  routine  use  in  very  low  birth  weight  babies  (15,24,34).  20% lipid emulsion is lower in phospholipids than 10% emulsion and thus likely  to result in better plasma clearance of trigycerides (35).

3.  Tolerance and risks of IV lipid

IV lipid tolerance is dependent on many factors, including gestation, rate of infusion,  the metabolic and growth status of the baby, and the preparation of lipid. Infusion of  lipid over 24 hours is better tolerated than intermittent infusion. Tolerance of IV lipid is  usually  assessed  by  measuring  plasma  triglycerides  but  there  is  little  evidence  to  define  normal  plasma  triglyceride  concentrations  in  the  newborn.  Hyperglycaemia  may be exacerbated by higher rates of lipid infusion, particularly in the smaller babies  (24,36)  but  historical  concerns  regarding  IV  lipid  and  hyperbilirubinaemia,  chronic  lung disease, impaired immune function, sepsis, altered platelet function, NEC, and  ROP have not been proven (31). Any potential risks of IV lipid are outweighed by the  benefits of early provision of essential fatty acids, particularly for the smallest babies

Recommendations for practice

• IV lipid should be given in addition to aqueous PN in a dose of 2 g/kg/day on the first  day  of  life  and  increased  daily  to  a  maximum  of  3.5  –  4  g/kg,depending  on  lipid  and glucose tolerance. It  is noted that  some  newer lipid formulations are licensed only to a dose of 3 g/kg/day.
• A 20% lipid emulsion is the preparation of choice; this should be continuously infused over 24 hours.

Micronutrients:

1.  Calcium, phosphate and magnesium

Calcium (Ca), phosphate and magnesium (Mg) are required for bone structure and  both muscle and nerve function. Ca should be provided in PN from day 1 to avoid  early  hypocalcaemia  secondary  to  delayed  secretion  of  parathyroid  hormone.  Organic  phosphate  compounds  should  be  used  in  PN  to  achieve  bone  mineral  accretion comparable to that in utero (11). 

Phosphate  requirements  are  likely  to  be  higher  when  protein  intake  has  been  maximised and growth optimised; phosphate and Ca should be provided to preterm  infants initially in a 1:1 molar ratio (26,37); subsequently higher doses of phosphate  may be required. A reasonable initial parenteral dose for all neonates would be 1.5  mmol/kg/day each of Ca and phosphate and 0.18 – 0.2 mmol/kg/day Mg.  

2.  Trace elements

Although  nutritionally  essential,  precise  requirements  for  trace  elements  in  the  premature neonate remain uncertain. Commercially available additions can only be  added to aqueous PN, although stable all-in-one neonatal PN solutions may become  available in the future (38). The addition of trace elements adversely affects the long- term stability of standard PN bags and so it is reasonable to commence standard,  unsupplemented  PN  solutions  out  of  hours,  with  trace  elements  added  to  the  first  routine PN fluid change. 

While most trace elements appear to be safe, IV iron carries a risk of oxidant injury  and is not recommended, at least for the first three weeks. Most neonates can be  managed with enteral iron supplements once PN has been discontinued  Further information on trace elements is summarised in Table 2, appendix.

3.  Vitamins 

Preterm infants are born with reduced stores of fat soluble vitamins and little, if any,  stores  of  water  soluble  vitamins.  Current  guidelines  for  vitamin  supplementation  of  preterm  infants  are  based  largely  on  expert  opinion,  with  most  data  obtained  from  small  historical  studies  of  moderately  preterm  babies  (11,39).  In  practice,  IV administration of fat and water soluble vitamins is limited by the availability of suitable multi-vitamin preparations.

Vitamin supplements must be added to PN fluids in a pharmacy aseptic unit. Ready mixed  lipid  and  vitamin  preparations  are  now  available;  a  decision  to  use  such products will need to consider convenience, safety and cost.

In the absence of evidence of efficacy or toxicity, it is recommended that both a fat and  a  water  soluble  multivitamin  preparation  be  added  to  PN  fluids  at  the  earliest practical opportunity. 

Recommendations for practice

• PN should  be  commenced  with  phosphate  and  Ca  in  a  molar  ratio  of  1:1, adjusted as required to maintain normal plasma Ca and phosphate. It is likely

that  higher  amounts  of  phosphate  will  be  required  for  the  smallest  preterm infants.

• Adjustment of Ca and phosphate levels in PN solutions should be undertaken with caution  as  there  is  potential  for  precipitation  of  salts.  More  soluble organic phosphate salts should be used.
• Neonatal PN  should  be  supplemented  with  trace  elements  using  a commercially available preparation in the manufacturer’s recommended dose as soon as practical after commencing PN.
• Both fat  and  water  soluble  vitamins  should  be  given  in  the  manufacturer’s recommended doses within 48 hours of commencing PN.
• Iron should  not  be  added  to  PN  fluids  except  in  those  infants  wholly  dependent on PN after 3 weeks of age. When iron has been added to PN,  serum ferritin should be monitored.

Practical considerations

Following  a  decision  to  start  PN,  consideration  must  be  given  to  prescription,  preparation  and  administration.  Safe  execution  of  each  of  these  steps  requires  a  multidisciplinary team including doctors, dietitians, pharmacists and other members  of the pharmacy team and nursing staff. Every stage of the process of providing PN  to a baby carries risks, all of which are discussed in the PCPG report (2). All neonatal  units providing PN should have access to pharmacy support, at least during regular  working hours, and protocols should be in place to meet the recommendations of the PCPG.

Prescription of PN: 

Initiation of PN in the neonatal unit (NNU) should follow locally agreed protocols. A  decision to initiate, or not to initiate, neonatal PN out with agreed criteria should only  be  made  by  an  experienced  healthcare  professional,  usually  the  senior  attending  clinician. As there is significant potential for error in prescription of PN, this should  only  be  undertaken  by  suitably  trained  persons  in  accordance  with  locally  agreed  guidelines.  Prescriptions  should  be  reviewed  daily.  Ideally  prescription  of  PN  will  involve a specialist neonatal pharmacist and a specialist neonatal dietitian as well as  the  clinician,  but  it  is  recognised  that  this  may  not  be  achievable  in  all  NNUs.  In  compiling local guidelines separate consideration should be given to the nutritional  and fluid requirements of the neonate, particularly in the first week of life, and both  specialist pharmacist and dietetic input must have been sought. When concentrated  PN  solutions  are  chosen,  guidelines  must  include  clear  and  comprehensive  instructions  for  manipulation  of  additional  fluids.  PN  and  total  fluids  should  be  prescribed based on birth weight until this has been exceeded; thereafter the baby’s  greatest recent weight should be used unless there is significant oedema.   Standardised  prescription  charts  reduce  the  likelihood  of  error,  and  electronic  prescribing eliminates the risk of transcription error. Standardised request forms for  PN  help  to  ensure  a  controlled,  validated  system  of  documentation  of  prescribing.  Any change in infusion rate from that on the label of the PN solution must be within  the  maximal  permitted  rate  of  infusion  for  the  solution,  and  must  be  clearly  documented on the patient’s PN prescription chart. The clinician who is accountable  for deciding upon the nutritional needs of the baby and the formulation of PN to be  administered should also sign the prescription. 

Compounding of PN:

The complexities of compounding of PN should not be underestimated. 

1.  Preparation and storage

PN  must  always  be  prepared  in  a  pharmacy  aseptic  unit.  PN  solutions  should  be  stored in a fridge when not in use, and allowed to reach  room temperature before  administration.  This  allows  the  solution  to  de-gas  and  reduces  the  likelihood  of  bubble  formation.  To  reduce  the  possibility  of  contamination  and/or  problems  with  incompatibility of additives and instability of solutions, changes must not be made to  PN formulations at ward level. Urgently required alterations to glucose or electrolyte  provision can be achieved without manipulating PN solutions.

2.  Additions to PN solutions

Drugs should not be added to PN solutions. The common practice of adding heparin  to PN affects lipid bonds and has not been shown to increase catheter patency so is  not  recommended  (40).  Additions  to  PN  solutions  must  not  be  made  outside  the  pharmacy aseptic unit.

3.  Standardised versus bespoke PN solutions

Standardised  PN  solutions  are  associated  with  lower  risk  of  compounding  and  prescribing  error,  and  will  be  suitable  for  a  vast  majority  of  neonatal  patients.  It  is  recommended  that  NNUs  and  networks  use  standardised  PN  bags  whenever possible, and that a decision to use a bespoke PN solution is only made by a senior  clinician, in conjunction with a specialist neonatal pharmacist and ideally a specialist  neonatal dietitian. It is recognised that specialist dietetic support is not available in all  NNU.  Suitable  PN  can  almost  always  be  provided  for  the  first  24  –  72  hours  by  having  24  hour  access  to  standardised  PN  solutions.  Several  standardised  formulations  of  neonatal  PN  are  currently  available  in  the  UK,  including  some  concentrated  formulae;  the  composition  of  locally  agreed  PN  solutions  should  be  regularly reviewed and reflect the results of properly conducted randomised clinical  trials with relevant safety data. Experience exists with glucose contents ranging from  7.2  to  16.7  g/100  mL  and  protein  ranging  from  2.0  to  3.8  g/100  mL  (2.3  –  4.3  g AA/100 ml).

  Administration of PN:

PN differs from simple glucose and electrolyte IV fluids in many regards including pH  and tonicity. The risks of extravasation injury and contamination are increased with  PN, and there is a need for enhanced biochemical monitoring. PN is an independent  risk  factor  for  neonatal  sepsis  and  catheter-associated  bloodstream  infection  (41).  Cost  is  also  an  important  factor,  added  to  by  dedicated  line  sets  and  specialised  filters. Wastage should be kept to a minimum. 

1.  Peripheral versus central lines

Ideally  PN  should  be  administered  via  a  central  line,  particularly  if  the  patient  is  expected to be PN dependent for more than a few days. In neonates this requires  either  a  properly  sited  umbilical  venous  catheter  or  a  peripheral  percutaneous  IV  central  catheter  (PICC).  Careful  attention  must  be  paid  to  maintaining  sterility  of  central lines both during and after insertion, and local protocols for line care should  be in place. Ideally a designated central line should be used exclusively for PN and  not accessed for blood sampling but it is recognised that this is not always practical  in  the  NNU  setting.  Local  policies  should  be  agreed  with  regard  to  insertion  and  management of central lines, and all staff trained accordingly. The reader is referred  to BAPM guidance on use of central venous catheters in the newborn (42). If other infusions are to run alongside PN then compatibility must be confirmed (11). Central  venous  line  position  must  be  confirmed  by  X-ray  before  use  (43).  The  preferred  position for the central line tip is either the inferior vena cava (ideally at level of the  diaphragm) or the superior vena cava (long-line only) (44), but it may not be possible  to insert PICC lines to this level. Atrial positioning should be avoided due to risk of  atrial perforation and cardiac tamponade (45). Even  when the position of a central line has been confirmed by X-ray, practitioners need to be aware of the possibility of  line migration.   Some NNUs will choose to administer PN via peripheral venous cannulae, often (but  not exclusively) as a short-term measure until central access can be achieved or to  maintain the delivery of nutrition while treating a central line-related infection.  When  PN is administered via peripheral cannulae the risk of extravasation injury needs to  be  balanced  against  the  risks  or  difficulties  associated  with  obtaining/maintaining  central  venous  access,  and  the  nutritional  needs  of  the  infant.  There  is  a  lack  of  consensus  around  the  maximum  osmolarity  of  IV  fluids  which  can  safely  be  administered  via  peripheral  cannulae;  recommendations  based  on  both  paediatric  and adult data vary from 600 – 900 mOsm/L. There is a dearth of neonatal studies.  Osmolarities  of  900  –  1000  mOsm/L  are  not  clearly  associated  with  higher  risk  of  line-related  events  although  redness  or  minor  swelling  at  the  peripheral  site  are  common;  only  one  significant  event  (marked  swelling,  blanching  of  area,  skin  necrosis or blistering and decreased or absent pulses below the site) was reported in  a total of 668 days of peripheral PN (46). Osmolarities greater than 1000 mOsm/L  have  been  associated  with  increased  complications  including  thrombophlebitis  and  infiltration  (47).  Infusion  of  lipid  via  the  same  peripheral  catheter  as  the  aqueous  component  may  have  a  vascular  protective  effect  (48).  PN  that  is  not  suitable  for  peripheral  line  administration  must  be  clearly  labelled:  ”to  be  given  by  central  line  only”; this is likely to include most concentrated PN solutions (2). The osmolarity of  12.5% dextrose is 630 mOsm/L.

2.   Commencement of PN infusion

Priming of lines and giving sets should be done under full aseptic conditions. A final  safety  check  at  the  point  of  administration  of  PN  should  be  performed,  including  checking the labels of PN solutions against the request form for: name of patient and  identifying number, route of administration (central or peripheral), date for infusion,  expiry date and appearance of the PN solution(s) (2). NNUs/networks should have  agreed  protocols,  and  ensure  that  staff  members  are  appropriately  trained  in  the  commencement of PN infusions

3    Filters, giving sets and infusion times

The use of in-line filters to reduce the risk of contamination of PN fluids by bacteria,  endotoxins  and  particulates  is  widely  practised  and  currently  recommended  by  ESPGHAN. Early data in adults suggested efficacy of in-line filters, but the practice is  increasingly being questioned, with no evidence of benefit in some recent studies in  both  adults  and  children.  There  is  a  paucity  of  evidence  in  neonatal  practice  (49).  There  are  two  main  IV  filter  pore  sizes;  the  0.22  micron  filter  used  for  aqueous  solutions, reported to remove air, microorganisms and particulate matter as well as  endotoxins released by gram-negative bacteria (50) and the 1.2 micron filter used for  larger  molecule  solutions  including  lipid.  Based  on  data from  two  studies  including  530 neonatal patients, use of in-line filters in central line giving sets changed every 96  hours  does  not  reduce  mortality  or  the  incidence  of  proven  or  suspected  septicaemia  compared  to  unfiltered  lines  changed  daily.  In-line  filters  are  cost  effective when IV fluids and giving sets are changed 96 hourly compared to 24 hourly  for  unfiltered  lines  (51).  Changing  PN  bags  48  instead  of  24  hourly  offers  considerable  cost  savings  and  does  not  result  in  increased  central  line-associated  blood  stream  infection  in  term  and  larger  preterm  infants  (52).  Extending  infusion  time for glucose and AA solution to 96 hours in association with in-line filter use may  be safe but this practice has not been directly compared with shorter infusion times  using the same filters. There is some evidence to suggest that it may be acceptable  to use lipid giving sets for 48 hours but rates of infection increase with 72-hourly lipid  giving set changes compared to 24 hourly. A pragmatic and safe approach would be  to change lipid syringes and giving sets every 24 hours (52,53). 

4.    Shielding from light

Light exposure is associated with peroxide generation in PN solutions which creates  oxidant  stress,  increases  degradation  of  vitamins  and  has  been  implicated  in  both  impaired  lipid  tolerance  and  slower  advancement  of  enteral  nutrition  (54,55).  In  a  recent  randomised  controlled  study,  protection  of  PN  solutions  from  light  was  not  associated  with  reduction  in  either  bronchopulmonary  dysplasia  or  death  (56).  Peroxide has bacteriostatic properties and so shielding PN solutions from light might  conceivably enhance the risk of late-onset sepsis but this has not been proven. On  balance, we recommend that all PN bags and giving sets should be protected from

light.

5.     Vitamin administration

Both  fat  and  water  soluble  vitamins  should  be  given  with  the  lipid  emulsion  to  improve vitamin stability and protect lipid preparations from peroxidation (54). Water  soluble vitamins may be added to aqueous PN if lipid is not being given. 

6.     Monitoring

Unexpected  biochemical  instability  as  a  consequence  of  PN  is  rare  but  may  have  serious consequences. Routine biochemical monitoring is generally accepted as best  practice and should take into consideration the duration of PN, infant gestation, co- morbidities  and  other  administered  medicines  (2).  The  individual  responsible  for  reviewing  biochemical  results  and  taking  appropriate  action  when  abnormal  values  are  observed  must  be  clearly  identified  on  a  daily  basis.  We  have  included  a  suggested schedule of monitoring based on ESPGHAN recommendations (11) which  should be implemented according to the baby’s clinical condition (Table 3, appendix).  Tolerance of IV lipid is usually assessed by measuring plasma triglycerides but there  is little evidence to define normal plasma triglyceride concentrations in the newborn.  Plasma triglyceride concentration > 3 mmol/L is common regardless of the amount of  lipid provision (24,32) and so it is reasonable to accept values of up to 3 mmol/L as within  normal.  Unwell,  septic  infants  are  more  likely  to  demonstrate  poor  lipid  tolerance. 

Low  selenium  status  has  been  implicated  in  oxidative  diseases  such  as  bronchopulmonary dysplasia and retinopathy of prematurity, but there is insufficient  evidence to recommend routine monitoring of plasma selenium levels (57). There is  no  need  to  monitor  trace  element  status  routinely  for  the  first  3  weeks  of  PN  treatment but for infants receiving long-term PN (defined as > 3 weeks with minimal  or no enteral feeds) additional monitoring on a monthly basis for trace element status  (including  copper,  manganese,  selenium  and  zinc)  and  fat  soluble  vitamin  status  should be considered. 

Recommendations for practice

• All NNUs/networks should have agreed protocols for the initiation of neonatal PN. Variation from protocol should only be made by a suitably experienced healthcare professional.

• Neonatal networks  should  aim  to  implement  standardised,  electronic  PN prescription charts.

• Additions to PN fluids should only be made in a pharmacy aseptic unit.

• Standardised PN solutions should be used whenever possible.

• PN should ideally be infused via a central line; the position of which must be confirmed  by  X-ray.  PN  formulations  with  an  osmolarity  greater  than  1000 mOsm/L should not be administered peripherally. 

• Commencement of PN infusions must be done under aseptic conditions, and with locally agreed checks in place to minimise error.

• Aqueous lines  used  with  0.22  micron  in-line  filters  may  safely  be  left undisturbed for up to 48 hours; lipid lines should be changed at intervals of 24 hours.
• Fat (and ideally water) soluble vitamins should be added to lipid emulsion, to improve vitamin stability.
• Regular biochemical  monitoring  of  neonatal  PN  patients  should  be undertaken, according to locally agreed protocol. 

Weaning PN

Appropriate minimal enteral feeds, preferably  maternal or donor breast milk should  be  given  in  conjunction  with  PN  wherever  possible  to  prevent  gut  atrophy  and  encourage gut adaptation, as well as reduce the risk of PN-associated liver disease.  Weaning of PN should be considered once the baby is stable and able to tolerate  some enteral feed. Weaning of PN should be described in local feeding guidelines  and both aqueous and lipid phases reduced proportionally as enteral feeds increase.  The rate of weaning will depend upon the baby’s clinical condition and may be limited  by  the  availability  of  maternal  expressed  breast  milk.  Care  needs  to  be  taken  to  ensure  that  electrolyte  requirements  are  met  as  the  volume  of  aqueous  PN  is  decreased; sodium may need to be added to milk or given as an oral supplement.  Occasionally  PN  will  need  to  be  continued  together  with  milk  feeds  for  prolonged  periods if milk tolerance is impaired. PN should generally be continued until at least  75% of nutritional requirement is tolerated enterally (58). For preterm babies after the  first few days of life, this would generally be a milk intake of at least 120ml/kg/day.   

Recommendations for practice

• Weaning of  PN  should  be  undertaken  according  to  locally  agreed  protocol  which ensures preservation of protein and energy intakes during the transition  phase. The policy should include a strategy for proportional reduction of all  macronutrients.

• PN should not normally be ceased until at least 75% of total daily nutritional requirements are provided via enteral feeds.

Audit of practice

All NNUs administering PN should have a programme for regular audit of practice.  Networks  and  individual  NNUs  should  be  aware  of  their  compliance  with  local  guidelines for administration of PN as well as incidence of PN-associated morbidities,  including sepsis and catheter complications. Equally importantly, the efficiency of PN  in  delivering  target  nutrition  should  be  regularly  reviewed  since  actual  provision  of  macronutrients  may  be  considerably  different  from  that  prescribed  and/or  intended  (58).    

Conclusions:

Neonatal  PN  is  an  essential  element  of  modern  neonatal  care  with  potential  to  influence  both  short  and  longer  term  outcomes.  All  neonatal  patients  in  the  UK  deserve  equal  access  to  PN,  prescribed  and  administered  according  to  carefully  considered local guidelines.  This Framework for Practice outlines how this may be  achieved.

Table 2: Recommended macro and micro nutrient intake for neonatal PN (11).

Table 3: Suggested monitoring of neonates receiving PN.

References:

1. Stewart JAD, Mason DG, Smith N, Protopapa K, Mason N, on behalf of CEPOD. A mixed bag; an enquiry into the care of hospital patients receiving parenteral.  2010  nutrition.  2010.  available  at  http://www.ncepod.org.uk/2010report1/downloads/PN summary.pdf.1a. Accessed  3/5/15  
2. Improving practice  and  reducing  risk  in  the  provision  of  parenteral  nutrition  for  neonates  and  children:  Report  of  the  Paediatric  Chief  Pharmacists  Group,  November  2011.  available  at    http://www.rpharms.com/support-pdfs/minimising- risk-pn-children-%286%29.pdf. Accessed 8/5/15  
3. Wood NS, Costeloe K, Gibson AT, Hennessy EM, Marlow N, Wilkinson AR. The EPICure study: growth and associated problems in children born at 25 weeks of  gestational age or less. Arch Dis Child Fetal Neonatal Ed 2003;88;F492-500  
4. Morgan C, McGowan P, Herwitker S, Hart AE, Turner MA. Postnatal head growth in  preterm  infants:  a  randomised  controlled  parenteral  nutrition  study.  Pediatr  2014;133:e120-8.   
5. Blanco CL.  Gong  AK  Schoolfield  J,  Green  BK,  Daniels  W,  Liechty  EA,  Ramamurthy R. Impact of early and high amino acid supplementation on ELBW  infants at 2 years. J Pediatr Gastroenterol Nutr 2012;54:601-7  
6. Cole TJ,  Statnikov  Y,  Santhakumaran  S,  Pan  H,  Modi  N,  on  behalf  of  the  Neonatal  Data  Analysis  Unit  and  the  Preterm  Growth  Investigator  Group.  Birth  weight and longitudinal growth in infants born before 32 weeks’ gestation: a UK  population study. Arch Dis Child Fetal Neonatal Ed 2014;99:F34-40  
7. Kuzma-O’Reilly B1,  Duenas  ML,  Greecher  C,  Kimberlin  L,  Mujsce  D,  Miller  D,  Walker  DJ.  Evaluation,  development,  and  implementation  of  potentially  better  practices in neonatal intensive care nutrition. Pediatr 2003;111:e461-70  
8. Peters O, Ryan S, Matthew L, Cheng, K. Randomised controlled trial of acetate in preterm neonates receiving parenteral nutrition. Arch Dis Child Fetal Neonatal Ed  1997;77:F12-F15  
9. Bauer J, Werner,C, Gerss. J. Metabolic rate analysis of healthy preterm and full- term infants during the first weeks of life. Am J Clin Nutr 2009;90:1517–24
10. Koletzko B, Poindexter B, Uauy R. Nutritional care of preterm infants : scientific basis and practical guidelines. Basel: S. Karger AG; 2014.
11. Koletzko B, Goulet  O,  Hunt  J,  Krohn  K,  Shamir  R.  Guidelines  on  Paediatric  Parenteral  Nutrition  of  the  European  Society  of  Paediatric  Gastroenterology,  Hepatology  and  Nutrition  (ESPGHAN)  and  the  European  Society  for  Clinical  Nutrition  and  Metabolism  (ESPEN),  Supported  by  the  European  Society  of  Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr 2005;41 Suppl 2:S1- 87.
12. Senterre T, Rigo  J.  Reduction  in  postnatal  cumulative  nutritional  deficit  and  improvement of growth in extremely preterm infants. Acta Paediatr 2012;101:e64- 70.  
13. Rochow N, Fusch  G,  Muhlinghaus  A,  Niesytto  C,  Straube  S,  Utzig  N  et  al.  A  nutritional program to improve outcome of very low birth weight infants. Clin Nutr  2012;31:124-31.  
14. Johnson MJ, Wootton  SA,  Leaf  AA,  Jackson  AA.  Preterm  birth  and  body  composition  at  term  equivalent  age:  a  systematic  review  and  meta-analysis.  Pediatr 2012;130:e640-9.  
15. Uthaya S, Liu  X,  Babalis,  D,  Dore  CJ,  Warwick  J,  Bell  J  et  al.  Nutritional  Evaluation and Optimisation in Neonates; a randomized double-blind controlled  trial  of  amino  acid  regimen  and  intravenous  lipid  composition  in  preterm  parenteral  nutrition.  Am  J  Clin  Nutr  e-pub  ahead  of  print  April  20,  2016  doi:  10.3945/ajcn.115.125138.  
16. Bottino M, Cowett  RM,  Sinclair  JC.  Interventions  for  treatment  of  neonatal  hyperglycaemia  in  very  low  birthweight  infants.  Cochrane  Database  Syst  Rev  2011;10:CD00745  
17. Stephens BE, Walden RV,  Gargus  RA,  Tucker  R,  McKinley  L,  Mance  M  et  al.  First-week  protein  and  energy  intakes  are  associated  with  18-month  developmental outcomes in extremely low birth weight infants. Pediatr 2009;123:  1337–43  
18. Arsenault D, Brenn M, Kim S, Gura K, Compher C, Simpser E. ASPEN clinical guidelines: Hyperglycemia and hypoglycemia in the neonate receiving parenteral nutrition. J Parenter Enteral Nutr   2012;36:81-95.   
19. Lafeber HN, van de Lagemaat M, Rotteveel J, van Weissenbruch M. Timing of nutritional interventions  in  very-low-birth-weight  infants:  optimal  neurodevelopment  compared  with  the  onset  of  the  metabolic  syndrome.  Am  J  Clin Nutr 2013;98:556S-60S  
20. Cormack BE, Bloomfield  FH.  Increased  protein  intake  decreases  postnatal  growth faltering in ELBW babies Arch Dis Child Fetal Neonatal Ed 2013;98:F399- 404.  
21. Mahaveer A, Grime  C,  Morgan  C.  Increased  early  protein  intake  is  associated  with  a  reduction  in  insulin-treated  hyperglycaemia  in  very  preterm  infants.  Nutr  Clin Pract 2012;27:399-405.  
22. Te Braake FWJ.  Van  den  Akker  CHP.  Riedijk  MA,  Goudoever  JB.  Parenteral  amino acid and energy administration to premature infants in early life. Sem Fetal  Neonatal Med 2007;12:11-18.   
23. Trevidi A, Sinn JKH. Early versus late administration of amino acids in preterm infants receiving parenteral  nutrition  (review).Cochrane  Database  of  Systematic  Reviews 2013: CD008771.   
24. Vlaardingerbroek H, Vermeulen  MJ,  Rook  D,  van  den  Akker  CHP,  Dorst  K,  Wattimena  JL  et  al.  Safety  and  efficacy  of  early  parenteral  lipid  and  high  dose  amino acid administration to very low birth weight infants J Pediatr 2013;163:638- 44.  
25. Burattini I, Bellagamba MP, Spagnoli C et al. Targeting 2.5 versus 4g/kg/day of amino acids  for  extremely  low  birth  weight  infants:  randomised  clinical  trial.  J  Pediatr 2013;163:1278-82  
26. Moltu SJ, Strommen K, Blakstad EW Almaas AN, Westerberg AC, Brække K et al. Enhanced  feeding  in  very-low-birth-weight  infants  may  cause  electrolyte  disturbances  and  septicaemia-  a  randomised  controlled  trial.  Clin  Nutr  2012;32:207-12.  
27. Blanco CL, Gong  AL,  Green  BK,  Falck  A,  Schoolfield  J,  Liechty  EA.  Early  changes  in  plasma  amino  acid  concentrations  during  aggressive  nutritional  therapy in extremely low birth weight infants. J Pediatr 2011;158:543-8.  
28. Morgan C, Burgess L. High protein intake does not prevent low plasma levels of conditionally essential  amino  acids  in  very  preterm  infants  receiving  parenteral  nutrition. J Parenter Enteral Nutr 2015   pii: 0148607115594009. [Epub ahead of  print]  
29. Moyses HE, Johnson MJ, Leaf AA, Cornelius VR. Early parenteral nutrition and growth outcomes in preterm infants: a systematic review and meta-analysis. Am J Clin Nutr 2013;97:816-26  
30. Lee EJ, Simmer K, Gibson RA. Essential fatty acid deficiency in parenterally fed preterm infants. J Paediatr Child Health 1993;29:51-55.
31. Salama GSA, Kaabneh MAF, Almasaeed MN, Alquran MIA. Intravenous IV lipids for preterm infants: a review. Clin Med Insights Pediatr 2015;9:25–36.   
32. Drenchpohl D, McConnell C, Gaffney S, Niehaus M, Macwan KS. Randomized trial of low birthweight infants receiving higher rates of infusion of intravenous IV  fat emulsions during the first week of life. Pediatr 2008:122:743-51.  
33. Rayyan M, Devlieger  H,  Jochum  F,  Allegaert  K.  Short-term  use  of  parenteral  nutrition  with  a  lipid  emulsion  containing  a  mixture  of  soybean  oil,  olive  oil,  medium-chain  triglycerides,  and  fish  oil.  A  randomized  double-blind  study  in  preterm infants. J Parenter Enteral Nutr   2012;36:81S–94S.  
34. Vlaardingerbroek H, Veldhorst M, Spronk S et al. Parenteral lipid administration to very-low-birth-weight infants—early introduction of lipids and use of new lipid emulsions: a systematic review and meta-analysis. Am J Clin Nutr 2012;96:255– 68.  
35. Haumont D , Deckelbaum  RJ,  Richelle  M,  Dahlan  W,  Coussaert  E,  Bihain  BE,  Carpentier  YA.  Plasma  lipid  and  plasma  lipoprotein  concentrations  in  low  birth  weight infants given parenteral nutrition with twenty or ten percent lipid emulsion.  J Pediatr. 1989 Nov;115(5 Pt 1):787-93.
36. van Kempen AA,  van  der  Crabben  SN,  Ackermans  MT,  et  al.  Stimulation  of  gluconeogenesis by intravenous IV lipids in preterm infants: Response depends  on fatty acid profile. Am J Physiol Endocrinol Metab. 2006;290:e723–e730.  
37. Bonsante F, Iacobelli S, Latorre G, Rigo J, De Felices C, Robillard PY, Gouyon B. Initial Amino  Acid  Intake  Influences  Phosphorus  and  Calcium  Homeostasis  in  Preterm Infants – It Is Time to Change the Composition of the Early Parenteral  Nutrition. PLoS ONE 2013 ;8:e72880.doi:10.1371/journal.pone.00728801.  
38. Parenteral Nutrition in a Neonatal Intensive Care Unit: Galenic Stability of Four All-in-one Admixtures,  E.Bourgier,  S.  Poullan-Termeu,  Eur  J  Hosp  Pharm  2015:22:285-290.    
39. Greene HL, Hambidge  KM,  Schanler  R,  Tsang  RC.  Guidelines  for  the  use  of  vitamins,  trace  elements,  calcium,  magnesium,  and  phosphorus  in  infants  and  children  receiving  total  parenteral  nutrition:  report  of  the  Subcommittee  on  Pediatric  Parenteral  Nutrient  Requirements  from  the  Committee  on  Clinical  Practice  Issues  of  the  American  Society  for  Clinical  Nutrition.  Am  J  Clin  Nutr  1988;48:1324-42.  
40. Berkow SE, Spear ML, Stahl GE, Gutman A, Polin RA, Pereira GR, Olivecrona T, Hamosh P,  Hamosh  M.  Total  parenteral  nutrition  with  intralipid  in  pr  Infants  Receiving TPN with Heparin: Effect c Lipolytic Enzymes, Lipids, and Glucose. J  Pediatr Gastroenterol Nutr 1987;6:581-588.  
41. Zingg W, Tomaske  M,  Martin  M.  Risk  of  parenteral  nutrition  in  neonates  –  an  overview. Nutrients 2012;4:1490-1503.  
42. http://www.bapm.org/publications/documents/guidelines/Use%20of%20Central% 20Venous%20Catheters%20in%20neonates.pdf. Accessed 6.12.15
43. Reece A, Ubhi  T,  Craig  AR,  Newell  SJ.  Positioning  long  lines:  contrast  versus  plain   radiography. Arch Dis Child Fetal Neonatal Ed 2001;84:F129-130.  
44. Rorke JM, Ramesthu  J.  Ch  31  Percutaneous  central  venous  catheterisation.  MacDonald  MG,  Ramasathu  J  (Eds)  2002;  Procedures  in  Neonatology  3 rd   Ed  Lippincott Williams and Wilkins Philiadelphia.  
45. Mirtallo J, Canada  T,  Johnson  D,  Kumpf  V,  Peterson  c,  Sacks  G,  Seres  D,  Guenter  P.  Safe  Practices  for  Parenteral  Nutrition.  J  Parenter  Enteral  Nutr   2004;28:S39-S70.    
46. Cies JJ, Moore WS. Neonatal and Pediatric peripheral parenteral nutrition: What is a safe osmolarity? Nutr Clin Pract 2014;29:118-124.
47. Dugan S, Le  J,  Jew  RK.  Maximum  tolerated  osmolarity  for  peripheral  administration  of  peripheral  parenteral  nutrition  in  pediatric  patients.  J  Parenter  Enteral Nutr 2014;38(7):847-851.  
48. Pineault M, Chessex P, Piedboeuf B, Bisaillon S. Beneficial effect of coinfusing a lipid emulsion on venous patency. J Parenter Enteral Nutr 1989;13(6):637-640.
49. Foster JP, Richards  R,  Showell  MG,  Jones  LJ.  Intravenous  IV  in-line  filters for  preventing  morbidity  and  mortality  in  neonates.  Cochrane  Database  of  Systematic  Reviews  2015,  Issue  8.  Art.  No.:  CD005248.  DOI:  10.1002/14651858.CD005248.pub3.   
50. Bethune K, Allwood  M,  Grainger  C,  Wormleighton  C;  British  Pharmaceutical  Nutrition  Group  Working  Party.  Use  of  filters  during  the  preparation  and  administration of parenteral nutrition: position paper and guidelines prepared by a  British pharmaceutical nutrition group working party. Nutrition 2001;17:403-8.  
51. Balegar VK, Azeem MI, Spence K, Badawi N: Extending total parenteral nutrition hang time  in  the  neonatal  intensive  care  unit:  is  it  safe  and  cost  effective?  J  Paediatr Child Health 2013;49:E57–E61.  
52. Fox M, Molesky  M,  Van  Aerde  JE,  Muttitt  S:  Changing  parenteral  nutrition  administration  sets  every  24  h  versus  every  48  h  in  newborn  infants.  Cana  J  Gastroenterol 1999;13:147–151.  
53. Matlow AG, Kitai  I,  Kirpalani  H,  Chapman  NH,  Corey  M,  Perlman  M  et  al.  A  randomized  trail  of  72-  versus  24-hour  intravenous  IV  tubing  set  changes  in  newborns receiving IV lipid therapy. Inf Control Hosp Epidem 1999;20:487-493.  
54. Silvers KM, Sluis KB, Darlow BA, McGill F, Stocker R, Winterbourn CC. Limiting light-induced lipid  peroxidation  and  vitamin  loss  in  infant  parenteral  nutrition  by  adding multivitamin preparations to Intralipid. Acta Pediatr 2001;90:242-9.   
55. Khashu M, Harrison  A,  Lalari  V,  Lavoie  J-C,  Chessex  P.  Impact  of  shielding  parenteral  nutrition  from  light  on  routine  monitoring  of  blood  glucose  and  triglyceride  levels  in  preterm  neonates.  Arch  Dis  Child  Fetal  Neonatal  Ed  2009;94:F111-115.  
56. Laborie S, Denis A, Dassieu G, Bedu A, Tourneux P, Pinquier D et al. Shielding parenteral nutrition  solutions  from  light:  a  randomised,  controlled  study.  J  Parenter Enteral Nutr 2015;39:729-37.   
57. Peirovifar A, Gharehbaghi MM, Abdulmohammad-zadeh H, Sadegi GH, Jouyban A. Serum selenium levels of the very low birth weight premature newborn infants with  bronchopulmonary  dysplasia.  Journal  of  Trace  Elements  in  Medicine  and  Biology 2013;27:317-321.  
58. Miller M, Vaidya R, Rastogi D, Bhutada A, Rastogi S. From parenteral to enteral nutrition: a  nutrition-based  approach  for  evaluating  postnatal  growth  failure  in  preterm infants. J Parenter Enteral Nutr 2014;38:489-97.  
59. Lapillonne A, Fellous L, Mokthari M, Kermorvant-Duchemin E. Parenteral nutrition objectives for very low birth weight infants: results of a national survey. J Pediatr Gastroenterol Nutr. 2009;48:618-26. 

[Rachel Phillips]

In addition to Naveed best reference; I would recommend as starter to review the appropriate use of PN and Neonatal Considerations (Attached ASPEN recommendation on the appropriateness of PN released in March, 2017). The review intended to guide evidence based decisions regarding appropriate PN use for all age group including Neonatal. Furthermore, attached clinical practice guideline; from Ireland and ASPEN review on optimizing PN for neonates.

Enhancing Parenteral Nutrition Therapy for the Neonate.pdf

Guideline-on-the-Use-of-Parenteral-Nutrition-in-Neonatal-and-Paediatric-Units.pdf

When PN is appro 0148607117695251.pdf

Hope this will help.

[Author]

Posts