Lin SHIH-YING2016.3.30

Gulide to Premature infant of nature

Outline

Definition

Epidemiology

Complication

Parenteral nutrition

Early enteral nutrition

Fortified human milk

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Defintions

Prematurity is defined as a brith that occurs before 37 completed weeks（less than 257 days）of gestation

Gestational age Birth weight 34~37 weeks Late preterm birth ＜2500g Low birth weight

＜32 weeks Very preterm birth ＜1500g Very low birth weight

≦28 weeks Extremely preterm birth

＜1000g Extremely low birth weight

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Epidemiology-Taiwan

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Epidemiology-WHO

About 15 million babies are born preterm each year; that is more

than 1 in 10 babies worldwide. 60% of them are born in sub-Saharan

Africa and South Asia

Around 1 million preterm babies die each year. an estimated

three-quarters of these preterm babies could survive

Though preterm births occur in high-income countries, access to

these proven interventions means that almost 9 out of every 10

pretrm babies survive in those settings in sharp contrast to about 1

out of 10 in low-income countries

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Complications

Hypothermia

Respiratory abnormalities

Cardiovascular abnormalities

Periventricular leukomalacia

Periventricular intraventricular hemorrhages

Necrotizing enterocolitis

Infection

Retinopathy of prematurity

Respiratory distress syndrome

ApneaPatent ductus arteriosus

Low blood pressure

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Summary list of WHO recommendations on interventions to improve preterm birth outcomes

Maternalinterventions

interventions Recommendations Strength of recommendation and quality of the evidencea

AntenatalcorticosteroidsTo improve Newborn outcomes

1.0. Antenatal corticosteroid therapy isrecommended for women at risk of preterm birth from 24 weeks to 34 weeks of gestation when the following conditions are met:�gestational age assessment can be accurately

undertaken;�preterm birth is considered imminent;�there is no clinical evidence of maternal infection�adequate childbirth care is available

( including the capacity to recognize and safely manage preterm labour and birth);

�the preterm newborn can receive adequate care if needed(including resuscitation, thermal care,

feeding support,infection treatment and safe oxygen use).

Strong recommendationbased on moderate-qualityevidence for newbornoutcomes and low-qualityevidence for maternaloutcomes

Tocolytics forinhibiting pretermlabour

2.0. Tocolytic treatments (acute and maintenancetreatments) are not recommended for women atrisk of imminent preterm birth for the purpose of

Conditional recommendation based on very low-quality

Summary list of WHO recommendations on interventions to improve preterm birth outcomes

Maternalinterventions

interventions Recommendations Strength of recommendation and quality of the evidencea

Continuous positive Airway pressure fornewborns with Respiratory distress syndrome

8.0. Continuous positive airway pressure therapy is recommended for the treatment of preterm newborns with respiratory distress syndrome.

Strong recommendationbased on low-qualityevidence

Surfactantadministrationfor newbornswith respiratorydistress syndrome

9.0. Surfactant replacement therapy isrecommended for intubated and ventilatednewborns with respiratory distress syndrome.

ConditionalRecommendation(only in health-care facilities whereintubation, ventilator care,blood gas analysis, newbonnursing care and Monitor ingare available) based onmoderate-quality

evidence

Oxygen therapyand concentration

10.0. During ventilation of preterm babies born at or before 32 weeks of gestation, it is recommended to

Strong recommendationbased on very low-quality

� Fetal genetic abnormalities� Fetal infection� Low prepregnancy weight,

poor gestational weight gain,malabsorption,malnutrition

� Confined placentalmosaicism

� Placental abnormalities

� Nutritional deficiencies� Condition after birth

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Parenteral Nutrition

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Goals of parenteral nutritionThe nutritional needs of premature infants are usually dependent upon parenteral

nutrition during early postnatal life,especially for very low birth weight(VLBW)

infants

The American Academy of Pediatrics recommends that growth of postnatal preterm infants in both their anthropometric indices and body composition should be the same as the normal fetus of the same gestational age.

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Nutritional Management

1. Early aggressive nutrition during te first several weeks after birth

when infants are at their most fragile(acute stage)

2. Fortified human milk or preterm formula for the intermediate

period when infants are commonly slowly advanced to full enteral

nutrition,but which could potentially represent an opportunity for

significant catch-up growth(growing care stage)

3. The postdischarge stage

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Total parental nutritionPN for the premature infant includes the following:

Adequate calories for energy expenditure and growth

VLBW:90~100kcal/kg/day ELBW:100-110kcal/kg/day

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GlucoseHigh glucose infusion rates（ 5 to 8 mg/kg per minute）may be requiredin the

preterm infant to prevent hypoglycemia because of the following:

1)Glucose is the primary energy substrate for the brain,which makes up a greater

proportion of body weight in preterm infants.This results in a higher glucose need.

2)Higher energy expenditure due to complications of prematurity such as respiratory

distress and hypothermia

Newborns with a plasma glucose concentration less than 45mg/dL in the first 24

hours after birth and afterwards;many clinicians use a threshold concentration of

less than 50mg/dL

ELBW are particularly susceptible to hyperglycemia:

Ineffective insulin secretion、End-organ insulin resistance、

Decreased glucose intracellular transporters、Provision for high glucose intakes

3.5mg/kg/minute 12mg/kg/minute（maximum）1~2mg/kg/minute

1.Insulin therapy2.Early initiation of

amino acid lipid infusion

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Amino acidsAn optimal mixture of essential/nonessential amino acids is required to achieve a

positive nitrogen balance,which results in protein acctrement and growth.

With no amino acid intake,VLBW infants lose about 1g/kg/day

Amino acid intake of 3.5~4g/kg/day，One review of the literature suggested ≧4g/kg/day

The essential amino acids in PN include :

isoleucine,leucine,lysine,methionine,phenylalanine,threonine,tryptophan and valine

In the premature infant,Cysteine,glutamine,glycine,histidine,taurine,and tyrosin

The ideal mixture of amino acid for PN in premature infants is unknown.Amino

acid solutions have been designed to based upon the composition of breast milk.

NPC/N=155~200:1

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LipidsIntravenous lipid administration provides essential fatty acids（ie,linoleic

and linoleic acids）that cannot be synthesized by humans,and is an

important nonprotein source of energy.

Fat emulson formulations used in premature infants contain varying combinations of soybean.safflower,or fish oil,with glycerin and egg yolk

phospholipids add as emulsifiers

We suggest initiate as a dose of 1g/kg/day and advance as tolerated to a

target of 3g/kg/day.A dose of 4g/kg/day occasionally is used.

10% VS. 20%﹖

Continous versus intermittent infusion﹖

LipofundinLipofundin ClinoleicClinoleic SmoflipidSmoflipid

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Gulide Tsang et al（（（（2005 ）））） ESPEN/ESPGHAN/ESPR guidelines,2005

Amino acids

Initiation,g/kg/day Day of birth Day of birth

Initial dose 2 ≧1.5

Target dose 3.5-4（ELBW） 3.2-3.8（VLBW） Maximum 4

Glucose

Initiation,g/kg/day Day of birth Day of birth

Initial dose 7 5.8-11.5

Target dose 13-17（ELBW） 9.7-15（VLBW） -

Lipids

Initiation,g/kg/day Day of birth（VLBW） Cautious support for ELBW No later than 3rd day

Initial dose ≧1 Linoleic acid＞0.25mg/kg/day

Target dose 3-4 3-4

Energy

Caloric target,g/kg/day 105-115（ELBW） 90-110 （VLBW） 110-120

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MineralELBW premature infants VLBW premature infants

第0天 過渡期 成長期 第0天 過渡期 成長期

Sodium（mEq） 0-1 2-4 3-7 0-1 2-4 3-5

Potassium（mEq） 0 0-2 2-3 0 0-2 2-3

Chloride（mEq） 0-1 2-4 3-7 0-1 2-4 3-7

Calcium（mEq） 20-60 60 60-80 20-60 60 60-80

Phosphorus（mEq）

0 45-60 45-60 0 45-60 45-60

Magnesium（mEq）

0 3-7.2 3-7.2 0 3-7.2 3-7.2

The intakes are limited by the solubility of Ca and P in PN solution:pH、amino acid concentration and source、temperature of the PN solution

Optimal ratio of Ca to P in PN is generally between 1.3-1.7:1

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Vitamins建議劑量建議劑量建議劑量建議劑量

(dose/kg/day)Maximum dose Lyo-povigen

A 500ug 700ug 3300 I.U

E 2.8mg 7mg 10mg

K 80ug 200ug 2mg

D 4ug 10ug 0.005mg

Ascorbic acid 25mg 80mg 100mg

Thiamin 350ug 1.2mg 3.9mg

Riboflavin 150ug 1.4mg 4.6mg

Pyridoxine 180ug 1mg 4.9mg

Niacin 6.8mg 17mg 40mg

Pantothenate 56ug 5mg 14mg

Biotin 6ug 20ug 0.06mg

Folate 56ug 140ug 0.4mg

Vitamin B12 0.3ug 1ug 0.005mg 22

Water&Electrolytes出生後天數出生後天數出生後天數出生後天數 建議攝取液體量建議攝取液體量建議攝取液體量建議攝取液體量（（（（ml/kg/day））））

第1天 第2天 第3天 第4天 第5天 第6天

Term infant 60-120 80-120 100-130 120-150 140-160 140-180

ELBW 60-80 80-100 100-120 120-150 140-160 140-160

VLBW 80-90 100-110 120-130 130-150 140-160 160-180

建議鈉、鉀、氯離子攝取量（mmol/kg/day）

Sodium 0-3(5)

Potassium 0-2

Chloride 0-5

In premature infants who receive PN,metabolic acidosis may commonly occura) Decreased renal reabsorption of bicarbonateb) PN solution,which contains amino acids（especially with the addition of

cysteine hydrochloride）,is usually acidic with a pH. Acetate as either a Na or K salt corrects and prevents the acidosis 23

Trace elementsPreterm Term Trace element（（（（1m

l））））Zinc 400 50-250 1500ug

Manganese 1 1 200ug

Copper 20 20 500ug

Selenium 1.5-2 2 -

Chromium 0.05-0.2 0.2 5ug

Iodine 1 1 28ug

Molybdenum 0.25 0.25 -

The only trace elements recommenses from the first day PN are zinc.The other trace elements are not needed until after two weeks of age.Iron is notneeded in the first few weeks after birth and is not routinely added to PN.

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MonitoringLaboratory test Frequency

Blood

Electrolytes：sodium,potassium,Chloride,bicarbonate

Daily until stable,then serially as indicated

Glucose Daily until stable,then serially as indicated

BUN,Creatinine,Calcium,phosphorus,Magnesium,alkaline phosphatase,Liver function

After the first week and then serially on an alternate week schedule as indicated

Urine dipstick Daily until stable,then serially as indicated

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Complication

Cholestasis-Cholestasis is a serious complication of PN and is manifested by jaundice due to a direct hyperbilirubinemia.

Infection and sepsis-Line infection is a common complication of PN in

premature infants.The two most common bacterial agents are

Staphylococcus epidermidis and Staphylococcus aureus.In the ELBW

infants,candidal infection have increased in frequency and are associated

with the administration of PN and the use of central venous catheters

Other line complications include infiltration，potentially skin sloughing，air embolus

Bone disease may occur if adequate nutrients are not provided

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Early enteral nutrition

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Early enteral nutrition當餵食量增加，進食耐受性較佳

需要靜脈營養的時期較短

與同時間使用靜脈營養的新生兒相比，發生conjugated hyperbilirubinemia的比例較低

少量進食14週後，鹼性磷酸酶活性遠低於第一週，特別是骨質鹼性

磷酸酶

可顯著刺激胃腸賀爾蒙，如胃泌素、胃抑素

Motility patterns較快成熟

鈣、磷吸收較佳

乳糖酶活性較好

降低intestinal permeability恢復體重所需時間較短

NPO天數較少、住院時間較短

不會增加NEC的發生率28

Early enteral nutritionGuidelines for early enteral enteral feeing are as follows：

feeding human milk；starting trophic feeding within 1-2 days of brith in

small volume as possible；monitoring gastric residual to guide increases of

feeding；not stopping feedings because of gastric residuals without signs

of NEC；and increasing feeds slowly by using feeding algorithm.

Human milk is initiated at 0.5ml/kg（10ml/kg/d）on day 1 if possible（at least within 3-5days），and advanced 10-20ml/kg/d as tolerated.The goal of feeding amount is 120-150ml/kg/day.Do not stop parenteral nutrition until enteral feeds are ＞90% of full

Human milk is initiated at 0.5ml/kg（10ml/kg/d）on day 1 if possible（at least within 3-5days），and advanced 10-20ml/kg/d as tolerated.The goal of feeding amount is 120-150ml/kg/day.Do not stop parenteral nutrition until enteral feeds are ＞90% of full

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Fortified human milk

Although humn milk is recommended for newborn infants for at least the first 6 months of life.

The calorie、protein、and minerals should be increasrd by adding

HMF to hunan milk

There is no definite guideline for when to start HMF

100ml/kg/day

initiallyOne packet is added to 50 ml（22kcal/oz or 75kcal/100ml）

One packet is added to 25ml（24kcal/oz or 81kcal/100ml）

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Fortified human milk

The low iron fortifier preserved the antibacteril activity of breast milk

against Escherichia coli，Staphylococcus，Group B Streptococcus

（GBS），and Cronobacter skazakii，and it can provide flexibility to add

iron as need.

HMF may be given 3600g until weight reaches or under the indication of

physician

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