Luís Pereira-da-Silva

Hospital de Dona Estefânia, CHLC, EPE

Faculdade de Ciências Médicas, UNL

Escola Superior de Tecnologia da Saúde de Lisboa, IPL

Braga, May 12th 2012

NUTRITIONAL ASSESSMENT

OF THE NEWBORN AND SMALL INFANT

Clinical, Biochemical and Body Composition Indicators

I. Clinical indicators (Anthropometry)

II. Biochemical indicators

III. Body composition

Methods for nutritional assessment

I. CLINICAL INDICATORS

(ANTHROPOMETRY)

Anthropometry as a method

Advantage: The most simple and inexpensive among

noninvasive methods convenient tool for bedside

evaluation Lafeber. Clin Perinatol 1999, Pereira-da-Silva in: Preedy ed.

Anthropometry, Springer 2012

Disadvantage: Indirect method with limitations inaccuracy

and non validated measurements in neonates De Bruin. AJCN

1995

Anthropometry – the interests

1. At birth: Diagnosis of fetal malnutrition anticipation of

early metabolic risk

2. Neonatal period and early infancy: Assessment of the

nutritional status (guiding the clinical practice)

3. Early indicators of late metabolic syndrome

(adolescence/ adulthood)

Pereira-da-Silva in: Preedy ed. Anthropometry, Springer 2012

Anthropometry - Measures

Direct measures: weight, length, head circumference

(HC), mid-arm circumference (MAC), skinfolds…

Derived measures: ponderal index, body mass index ,

MAC:HC ratio, mid-arm cross sectional areas…

Pereira-da-Silva in: Preedy ed. Anthropometry, Springer 2012

Weight

The most used measure

High accuracy and reproducibility

Incubators with incorporated

scale

However – the body weight

does not give any information on

body compartments and quality of

growth

Gibson. Horm Res 2003

To be used:

At birth reflecting intrauterine nutrition

First postnatal weeks (preterm infant) evaluation of

the nutritional support

First postnatal months (preterm infant) evaluation

of medium- long-term growth

Weight

Reference curves

Weight

Fetal malnutrition and early metabolic risk Olsen IE, et al. Pediatrics 2010;125:e224

Reference values at birth for: weight, length and HC< > gestational age < >

gender; centiles 3 to 97

Small for-gestational-age (SGA) risks: hypothermia, hypoglycemia,

hypocalcemia, necrotizing enterocolitis (preterm)

Large for-gestational-age (LGA) risks: hypothermia, hypoglycemia,

polycithemia

Constitutional SGA and LGA

Birth weight BMI in adulthood

Curhan. Circulation 1996

Cohort USA: 71.100 neonates 22.846 men at 56 yr J shape curve

Undernutrition Overnutrition

BMI

Weight Nutritional assessment – At birth

Olsen IE, et al. Pediatrics 2010;125:e224

x

E.g.: 32 wks, BW1000, < centile 3 equivalent to < -2SD

z-score calculation: 1823–1000 = 823; 823:306 = -2,68 SD

Weight

Nutritional assessment – First postnatal weeks

Reflect the current clinical

assistance (12 NICUs in USA)

Include: weight, length, HC and

mid-arm circumference

Specific reference values for

SGA, and main comorbidities

(HMD, NEC, BPD…)

http://pediatrics.aappublications.org/cgi/content/full/104/2/280

Ehrenkranz. Pediatrics 1999;104:280

Weight

Nutritional assessment – First postnatal months

Useful for postdischarge follow-

up (up to 50 weeks corrected GA)

– curves for weight, length (lean

mass, and HC (brain)

http://www.biomedcentral.com/1471-2431/3/13 Fenton TR. BMC Pediatr 2003;3:1

Length

Rough indicator of the lean mass; Reflects the skeleton growth Koo. J

Nutr 2000; Gibson. Horm Res 2003

The accurate measurement is of utmost importance when length is

included squared or cubed in indices (BMI, ponderal index)

However Accurate crown-heel length measurement is not easy in

neonates, specially in full-term neonates

Length measurement technique

Conventional method: difficulty in

extending the lower limbs

accuracy reaction to the

discomfort (Neonatal Facial

Coding System) caused by full

extension - equivalent to heel

prick

Pereira-da-Silva. Acta Paediatr 2006

Validation of an alternative method

Length measurement technique

Length measurement technique

Alternative method:

Extending only one lower limb

(the trunk axis should be at a right

angle with the line between the

ileac crests)

Easer, maintains the accuracy

while reducing significantly the

discomfort

Pereira-da-Silva. Acta Paediatr 2006

Head circumference (HC)

Reflects the growth of the brain

the HC is reduced in

cases of severe and

prolonged intrauterine

undernutrition.

Freedman. Science 1980

Mid-arm circumference (MAC)

Reflects the combined arm

muscle and fat compartments

indirect indicator (with limitations)

of the body fat and protein

reserve Georgieff. Clin Perinatol

1986

Pereira-da-Silva in: Preedy ed. Anthropometry,

Springer 2012

Skinfolds

Estimate the subcutaneous fat,

assuming that the measured sites

represent the average thickness of

the subcutaneous fat layer

More used skinfolds: triceps and

biceps (peripheral fat),

subscapular and suprailiac (trunk

fat)

Lukaski. Am J Clin Nutr 1987

Pereira-da-Silva in: Preedy ed.

Anthropometry, Springer 2012

Skinfolds

Male TS

(mm)

BS

(mm)

SBS

(mm)

SPS

(mm)

GA

(wks)

Mean SD Mean SD Mean SD Mean SD

32-33 2.59 0.58 2.31 0.63 2.49 0.56 1.73 0.52

34 3.07 0.70 2.42 0.69 2.89 0.80 2.20 0.67

35 3.25 0.61 2.61 0.62 3.03 0.64 2.30 0.63

36 3.44 0.84 2.77 0.79 3.25 0.78 2.53 0.75

37 4.05 0.98 3.46 0.91 3.77 1.01 3.15 0.85

38 4.03 0.85 3.47 0.83 3.69 0.80 3.17 0.76

39 4.21 0.84 3.61 0.89 3.92 0.90 3.32 0.76

40 4.23 0.83 3.63 0.83 3.95 0.85 3.35 0.74

41 4.26 0.88 3.68 0.77 3.94 0.79 3.43 0.78

Rodriguez. Eur J Pediatr 2004

Central to total skinfold

ratio (CTS)

CTS = (SPS+SBS)/

(TS+BS+ SPS+SBS)

Estimates the central

(troncular) fat

CTA – Not validated

yet

GA

(wks)

Male Female

32-33 47.24±3.93 48.70±4.14

34 47.87±3.73 48.80±4.16

35 47.55±3.18 49.17±3.02

36 48.28±3.24 49.03±3.08

37 47.87±3.01 49.48±3.05

38 47.64±3.12 48.71±3.09

39 48.04±3.25 48.76±3.30

40 48.17±3.06 49.15±3.47

41 48.13±3.19 49.06±3.52

Rodriguez. Eur J Pediatr 2004

Skinfolds

As indicators of total body fat (TBF):

Good correlation (DEXA) Schmelzle. Am J Clin Nutr 2002; Koo. Pediatr

Res 2004; Ahmad. Am J Hum Biol 2010

Poor correlation (MRI) Lapillonne. J Pediatr Endocrinol Metab 1999;

Olhager. Acta Paediatr 2006

Skinfolds

Limitations in estimating the TBF in neonates:

Do not reflect the non-subcutaneous fat; TBF = subcutaneous fat + non-

subcutaneous fat (intrabdominal)

Rapid changes in fat distribution during the neonatal period

The hydration status affects the skinfold compressibility

Accurate measurement requires skill and training (high inter-observer

coefficient of variation)

Skinfolds

Prins. Pediatric Rev Commun 1995

Pereira-da-Silva in: Preedy ed. Anthropometry, Springer 2012

Derived Measures

Certain indexes and formulas associate direct measures and are

capable to predict the body composition and the nutritional status

better than each value on its own

WHO Tech Rep Ser. 1995

INDEXES

based on Weight and Length

1. Ponderal index (W / L3) x100

2. Adiposity index – Body mass index (W / L2)

3. Weight/ Length ratio (W / L)

4. Benn index (W / Ln)

5. Individualized Weight/ Length ratio

Tamim. J Perinat Med 2004

Ponderal index (IPI) W / L3 x100

Used to define types of IUGR:

Late IUGR in gestation – only

weight affected Low PI:

Asymmetrical IUGR

Early IUGR in gestation –

weight + length affected

Normal PI : Symmetrical

IUGR

Normal neonate

Normal PI

Low PI

Asymmetrical IUGR

Normal PI

Symmetrical IUGR

G A40 weeks, ♂

BW 2400 g (SGA)

Length 49 cm

PI = 2.0

Weight (g) x 100/ Length3

(cm)

Asymmetrical IUGR

Lehingue. Am J Hum Biol1998

X

Ponderal index

Type of IUGR

Asymmetrical IUGR – risk

of: asphyxia,

hypothermia,

hypoglycemia and

hypocalcemia

Fay. Aust N Z J Obstet Gynecol

1991

(neonate on the right)

Ponderal index

Symmetrical IUGR - risk of:

poor neurodevelopment and

growth outcome

Berg. Early Hum Dev 1989

Causes: Early and prolonged fetal

malnutrition; Intrauterine infection;

Toxics / Drugs;

Cromosomopathies; Syndromes;

Constitutional

Ponderal index

Type of IUGR

Mid-arm circumference / Head circumference

(MAC:HC ratio)

The HC is used in the denominator as constant, assuming that in

acute protein-energy malnutrition the brain is relatively spared

compared to muscle and fat wasting Freedman. Science 1980

MAC: reflects an acute consumption of fat and protein Sasanow. J

Pediatr 1986

MAC:HC ratio

Fetal malnutrition and early metabolic risk

MAC:HC

Especially useful in diagnosing

malnourished AGA neonates

who would be not identified as

IUGR by the criterion exclusively

based on BW (still > 3rd centile)

Patterson. Am J Obstet Gynecol

1987

MAC:HC

Better indicator of early

metabolic risk and

Hypothermia than the PI

Chang. Early Hum Dev

1993

GA

(weeks)

MAC (cm) MAC:HC

Mean SD Mean SD

25-26 4.9 0.7 0.22 0.02

27 5.25 0.3 0.22 0.01

28 5.5 0.5 0.23 0.02

29 5.7 0.4 0.23 0.02

30 6.0 0.7 0.23 0.02

31 6.4 1.0 0.23 0.03

32 7.0 0.5 0.24 0.02

33 7.0 0.8 0.24 0.02

34 8.3 0.5 0.27 0.01

35 8.1 0.6 0.26 0.01

36 8.3 0.6 0.26 0.02

37 9.5 0.7 0.28 0.02

38 9.5 0.7 0.28 0.01

39 9.7 0.9 0.28 0.02

40 10.1 0.6 0.29 0.02

41 10.2 0.6 0.29 0.02

42 10.6 0.5 0.30 0.01

Sasanow. J Pediatr 1986

MAC:HC ratio

Fetal malnutrition and early metabolic risk

(Barker theory)

FETAL MALNUTRITION

Permanent intrauterine structural and functional changes

(“programming”)

Neonatal anthropometric indicators: fetal malnutrition

+

Postnatal anthropometric indicators: fast catch-up growth

Insulin resistance

Obesity, cardiovascular disease, hypertension, dyslipidemia,

diabetes 2

LATE METABOLIC SYNDROME

Late Metabolic Syndrome

Anthropometry at birth

WEIGHT

<1500g and <1000g risk of glucose intolerance and late metabolic

syndrome (MS) Barker. Diabetologia 1993, Pandolfi. Metabolism 2008

SGA and Macrosomy risk of late MS McCance. BMJ 1994, Wang.

Indian J Pediatr 2007

<2500g + fast catch-up growth 0-6 months Hypertension in adulthood

McCarthy. Pediatr Res 2001

SGA + fast catch-up growth 0-3 years insulin resistance + central

adiposity Soto. J Clin Endocrinol Metab 2003, Mericq. Diabetologia 2005

Late Metabolic Syndrome

Anthropometry at birth + Anthropometric evolution

Asymmetrical SGA +

Fast catch-up growth fast catch-up growth 0-2 anos BMI, central

adiposity and hypertension at age of 5-8 years Ong. BMJ 2000, Singhal,

Circulation 2006

Adiposity spurt (BMI) 7-15 years coronary disease in adulthood

Eriksson. BMJ 1999

Late Metabolic Syndrome

Anthropometry at birth + Anthropometric evolution

Term AGA neonates +

Fast weight gain 0-6 months (but not at 3-6 years) risk of

metabolic syndrome (waist circumference, blood pressure,

triglycerides, HDL, glicemia, insulinemia) at age of 17 years,

independently of BW Ekelund. J Clin Endocrinol Metab. 2007

Late Metabolic Syndrome

Anthropometry at birth + Anthropometric evolution

Mid-arm Cross Sectional Areas

Equations based on mid-arm circumference (MAC) and tricipital skinfold

(TS) estimate total arm area (AA), arm muscle area (AMA) and

arm fat area (AFA):

AA= MAC2 / 4; AMA = (MAC– TS) / 4; AFA= AA- AMA Jelliffee. J

Trop Pediatr 1969

AFA = MAC.TS/2; AMA = AA – AFA Rolland-Cachera. AJCN 1997

For the same mid-arm circumference (MAC):

Case 1 Case 2

Fat area 1 > Fat area 2 Muscle area 1 < Muscle area 2

Mid-arm Cross Sectional Areas

May be better indicators of the relative contribution of fat and muscle in total arm

area, than the isolated values of MAC and TS

Georgieff. J Pediatr 1989, Hediger. Pediatrics 1998

Correlation with body composition in:

In adults (CT scan). Heymsfield. Am J Clin Nutr 1982

In adolescents and children > 9 years (MRI). Rolland-Cachera. AJCN

1997

In neonates (DEXA). Koo. Pediatr Res 2004

Mid-arm Cross Sectional Areas

In neonates and small infants:

Reference values published. Sann. Arch Dis Child 1988

Frequently used in nutrition assessment. Georgieff. J Pediatr 1989,

Hediger. Arch Pediatr Adolesc Med. 1998

Mid-arm Cross Sectional Areas

In neonates and small infants:

Regional anthropometry (eg, mid-arm) as indicator of whole body

composition Consistency questioned: regional anthropometry

also will allow the estimate of the composition of the interested

region (eg, mid-arm)

Mid-arm Cross Sectional Areas

Anthropometry versus Ultrasound: term neonates

Mid-arm Cross Sectional Areas

Healthy term neonates:

Anthropometry

Poor correlation with the

ultrasound measures

Overestimate muscle area

muscular (±110%) and

underestimate fat area (±35%).

However, both methods have

limitations…

Pereira-da-Silva. Early Hum Dev 1999

Mid-arm Cross Sectional Areas

Anthropometriy versus MRI: preterm infants

Mid-arm Cross Sectional Areas

Preterm infants:

Anthropometry

Compared with magnetic

resonance measurements

Direct and derived measures –

non reliable predictors (r2<0.56) of

the mid-arm compartments

Pereira-da-Silva. Neonatology 2009

Mid-arm Cross Sectional Areas

Mid-arm Anthropometry

To summarize, neonates and small infants:

Simple, noninvasive, non expensive and convenient method

(bedside tool)

Useful in individual longitudinal measurements

Other measurements: interpret with caution

II. BIOCHEMICAL INDICATORS

Protein markers

1. Prealbumin

Neonate: term 4-20 mg/dl; preterm 4-14 mg/dl

Half-life ±24 h (albumin 14-20 days)

Limitations: in preterms hepatic synthesis and turnover

Polberger. Acta Paediatr Scand 1990 ; Anderson. Clin Perinatol 2002

2. Retinol binding protein

1-7,8 mg/dl

Half-life 12 h

Specific vitamin A binding proetin; circulates in plasma bound to

prealbumin

Limitations: affected by hepatic dysfunction, infections,

corticotherapy, renal diseases

Protein markers

3. BUN

7-22 mg/dl

It is not an indicator of protein reserve, however may reflect the

intake of protein (specially if insufficient)

Moro. J Pediatr Gastroenterol Nutr 1995

Protein markers

1. Blood markers

Hypophosphatemia (<4mg/dl), hypocalcemia and high alkaline

phosphatase (>800 IU/ml) – poor correlation with BMC

assessed by DEXA in preterm infants Faerk. ADC Fetal Neonatal

Ed 2002

Bone markers

2. Urine markers

Urinary excretion of Ca and P - Tubular rebsorption of phosphate

(TRP) - good guide for phosphate supplementation; if >95%

inadequate supplementation

%TRP = 1 − (PU/CrU) x (CrU/Pp) x 100

P = phosphorus; Cr = creatinine; U = urine; p = plasma

Harrison. Acta Paediatr 2008

Bone markers

3. Urine markers

Urinary Ca and P : creatinine ratios

Reference values: 95th centile: CaU:CrU = 3.8 mmol/mmol; PU:CrU =

26.7 mmol/mmol Aladangady. Pediatr Nephrol 2004

Standard reference - limited usefulness: ratios highly depend on

type of feed (HM, formula…) and not validated (DEXA) Harrison.

Acta Paediatr 2008

Bone markers

Hematological markers

Fe and folic acid hemogram, ferritin, transferrin

Growth Factors

Proteins binding to receptors of cell membranes activate

proliferation and differentiation

Depend on the nutritional status

Permit the evaluation of growth and nutritional status

Usually limited to research

Growth Factors

1. Insuline growth-like factor 1 (IGF-1)

1. Before known as somatomedin C

Released by the liver in response to the GH

Positive correlation with the gestational age and the energy

and protein intake

Kajantie. Pediatr Res 2001, Moyer-Mileur. Clin Perinatol 2007

Growth Factors

2. IGFBP-3

Main IGF-1 binding protein (among 6)

Allows a better interpretation of IGF-1 values

Kajantie. Pediatr Res 2001, Moyer-Mileur. Clin Perinatol 2007

Growth Factors

3. Leptin

Protein secreted by the adipocyte “signals” the brain on

energy reserve status

Positive correlation with : amount if stored fat, birth weight,

BMI, insulinemia andIGF-1

↓ leptinemia – undernourished preterm infants

Ng. Clin Endocrinol 2001, Moyer-Mileur. Clin Perinatol 2007

III. BODY COMPOSITION

Levels of Body Composition

5 Levels

Wang. AJCN 1992

Levels of Body Composition Neonate

Model of 2 or 3 levels: less informative, but more practical and feasible

Rigo. Nestle Nutr Workshop Ser Pediatr Program 2006

Body mass (weight) = Fat mass FM + Fat free mass FFM (+ Bone

mass)

Terminology

FFM = Lean mass + non-fat components of the adipose tissue

FM = pure fat

Adipose tissue = FM + cellular structures and non-cellular structures

of support

Body composition Noninvasive methods of assessment

more used

I. Magnetic resonance imaging (FM + FFM)

II. Dual energy x-ray absorptiometry (DEXA) (FM + FFM + bone mass)

III. Air displacement plethysmography (FM + FFM)

IV. Bioimpedance analysis (FM + FFM)

V. Anthropometry (FM + FFM)

VI. Others: total-body electrical conductivity (TOBEC), infrared

spectroscopy (FM + FFM) …

I. Magnetic resonance imaging

Gold standard in the measurement of adipose tissue (high precision,

fat volumetry), validated in preterm infants Olhager. Pediatr Res 1998,

Harrington. Lipids 2002

Limitations: very expensive, require motionless / sedation, and

displacement of the patient into the equipment Used for research

and validation of less accurate methods Rigo. Nestle Nutr Workshop Ser

2006

Regional assessment - “quality” of fat

Neonates ≤32 weeks

Normal evolution: postnatal

acceleration of growth total and

subcutaneous fat

Severe disease: deep intra-

abdominal fat risk of insulin

resistance

Uthaya. Pediatr Res 2005

I. Magnetic resonance imaging

II. Dual energy x-ray absorptiometry (DEXA)

3-compartment model: FM, FFM and bone mineral content

Good reproducibility in neonates and small infants Godand. J Clin

Densitom 2010

Rapid (6–10 min); non requiring sedation Rigo. Nestle Nutr Workshop

Ser 2006

Limitations:

Reliability questioned in small

individuals requiring validation

Lapillonne. Horm Res 1997, Koo. J Am Coll

Nutr 2004

Expensive, requires displacement of

the patient into the equipment Rigo.

Nestle Nutr Workshop Ser 2006

II. Dual energy x-ray absorptiometry (DEXA)

III. Air displacement plethysmography

(Pea Pod®)

2-compartment model: FM, FFM

Density = Mass/ Volume; %MG = (495/

density) - 450

Validated in neonates and small infants (1-

8 Kg) Ma. AJCN 2004

Advantages: Movable equipment; rapid (4-

5 min); movements allowed Rigo. Nestle

Nutr Workshop Ser 2006

Limitation: Expensive and does not

measure regional fat

Nutrition Lab, H. D. Estefânia

42 days of life,

weighing =1412 g

Enfalac AR® 14%

Miltina Prem® ( energy

and protein) thickened

121 136 Kcal/Kg/d

Prot 3 4,3 g/Kg/d

1 week later:

49 days of life,

weighing =1569 g

(+157 g)

III. Air displacement plethysmography

(Pea Pod®)

A.

Fat free mass

1364 g (96,6%)

Fat mass

47,8 g (3,4%)

B. 1 week later

Fat free mass

1569 g (91,8%)

Fat mass

141 g (8,2%)

III. Air displacement plethysmography

(Pea Pod®)

IV. Bioimpedance analysis

2-compartment model: FM, FFM

Portable equipment (tetrapolar),

allows movements, relatively

inexpensive, bedside use Rigo. Nestle

Nutr Workshop Ser 2006

Not validated in neonates and small

infants… Dung. Eur J Pediatr 2007

NICU, Hospital Dona Estefânia, Lisbon

V. Quantitative Ultrasound

Bone compartment

Convenient method: Noninvasive,

portable equipment , allows

movements, relatively inexpensive,

bedside use

Measures the bone strength; Unit of

measure : speed of sound (SOS) m.s-1

Littner. J Pediatr Endocrinol Metab 2003

NICU, Hospital Dona Estefânia, Lisbon

In neonates and small infants

Standardized method but not validated yet Littner. J Pediatr Endocrinol

Metab 2003

QUS cannot be used as a surrogate for DEXA; however, both

methods may complement each other in the assessment of bone

health Gianni. Arch Dis Child Fetal Neonatal Ed 2008

V. Quantitative Ultrasound

Bone compartment

I. Clinical indicators (Anthropometry)

Anthropometry – the most used method – however it is usually

limited to weight evolution…

Urgent validation of more measurements

Summary

Nutrition Assessment of the Neonate

II. Biochemical indicators

– Energy, protein and bone markers: several limitations,

especially in preterm infants

– Hematological markers – useful in clinical practice

– Growth factors – useful in research

Summary

Nutrition Assessment of the Neonate

III. Body composition

MRI: gold standard, volumetric measurements, used in research

and for validation of other methods

DEXA: 3-comparment model (+ BMC), good reliability, but validity

questioned in small individuals

ADP (Pea Pod): 2-comparment model, promising method, but

does not measure regional fat

Summary

Nutrition Assessment of the Neonate

III. Body composition

QUS: bone compartment (bone strength), promising method

Bioimpedance analysis: 2-comparment model, convenient,

relatively inexpensive, but not validated

Summary

Nutrition Assessment of the Neonate

Clinical practice, tools usually available in NICU

Daily weight; weekly: length and HC

BUN to monitor protein intake (weekly or every 2 wks)

Phosphatemia and alkaline phosphatase to monitor bone

nutrition (weekly or every 2 wks)

Hemogram and ferritin to monitor iron and folic acid intake

(every 2 wks)

Check long bones in x-rays

Suggestion

Thank you