Growth and Development

Intrauterine growth and nutrient accretion

Body Composition Growth Assessment

Growth Charts Patterns Alterations in Growth

Development Metabolic Physiologic neurologic

Growth

Growth

A normal, healthy child grows at a genetically predetermined rate that can be compromised by imbalanced nutrient intake

Growth

Growth is a dynamic process defined as an increase in the physical size of the body as a whole or any of its parts associated with increase in cell number and/or cell size

Reflects changes in absolute size, mass, body composition

Undernutrition

⇩⇩ weight ⇒⇒⇩length or height Underweight ⇒⇒ proportionate

Fetal Growth from 25-40 weeks GA

Weight increases 4-fold Length and OFC increase 2-fold

Body Composition Fat accounts for 0.5% of body weight

at the fifth month of fetal growth and 16% at term.

3rd trimester: increase from 1-3% of body weight to 10-16% of body weight at term

Minerals

Two-thirds of mineral content of full-term newborn is accummulated in the last trimester of pregnancy.

Age-related changes in body composition. (Reprinted by permission ofMosby Year Book. Heird WC, Driscoll JM, Schullinger JN, et al.Intravenous alimentation in pediatric patients. J Pediatr 80:351, 1972.)

Energy Reserves

Birthweight Non protein kcal Total kcal

500 50 225

800 grams 125 435

1000 grams 165 600

1500 425 1120

2000 1050 1975

3500 4175 5924

Determinants of fetal growth

Genetics Maternal/paternal genes, race, sex

estimated to account for 20% of variance in birth weight

Environmental factors

Environmental factors Maternal health Nutrition

Glucose, fatty acids, amino acids for tissue deposition and fuel for oxidative purposes

Ability of maternal-placental system to transfer nutrients to fetus

Endocrine environment E.g. LGA infant:

glucose-insulin-growth factors

Individual Growth Patterns

Weight and length at term appear to be primarily determined by nongenetic maternal factors

Birth weigh and birth length weakly correlate with subsequent weight and length values

Individual Growth Patterns, cont.

African American males and females are smaller than whites at birth, but they grow more rapidly during the first 2 years

Patterns of growth in breastfed infants are different from formula fed infants

GROWTH IN FIRST 12 MONTHS From birth to 1 year of age, normal human

infants triple their weight and increase their length by 50%.

Growth in the first 4 months of life is the fastest of the whole lifespan - birthweight usually doubles by 4 months

4-8 months is a time of transition to slower growth

By 8 months growth patterns more like those of 2 year old than those of newborn.

Body Composition BMI and percentage of body weight

made up of fat increase rapidly during the first months of life After birth, fat accumulates rapidly

until approximately 9 months of age

Weight Gain in Grams per Day in One Month Increments - Girls

Age 10th

percentile50th

percentile90th

percentileUp to 1month

16 26 36

1-2months

20 29 39

2-3months

14 23 32

4-5months

13 16 20

5-6months

11 14 18

Guo et al., J Peds. 1991

Weight Gain in Grams per Day in One Month Increments - Boys

Age 10th

percentile50th

percentile90th

percentileUp to 1month

18 30 42

1-2months

25 35 46

2-3months

18 26 36

3-4months

16 20 24

4-5months

14 17 21

5-6months

12 15 19

Guo et al., J Peds. 1991

Weight gain of Breast fed vs bottle fedinfants: 8-112 days of age (g/d)

Breast fed Bottle fed

Male 29.8 + 5.8 32.2 + 5.6

Female 26.2 + 5.6 27.5 + 4.9

Nelson et al Early Human Development 19:223 1989

Rates of gain for breastfed and formula fed infants during early months of life generally have been found to be similar although some reports have demonstrated greater gains by breastfed infants and others have shown greater gains by formula fed infants

Assessment

Screening identifies nutritional risk and/or need for further assessment. Underweight Overweight Failure to grow “over fat”

Reference vs Standard

Reference: a set of data used for normalizing measurements so that they can be manipulated statistically, grouped and compared with other sets of measurements. In principle, implies no value judgement and tells us nothing about optimal or satisfactory growth

Standard: Implies a value judgement. In theory, standards are selected based on representing “optimal”, “normal” or “goal”

Fetal/Neonatal Growth Charts

Intrauterine charts Classification of newborn

AGA LGA SGA

Postnatal Charts

Intrauterine/Fetal Growth Standards

Lubchenco Gairdner Babson Benda Fenton Olsen

Fetal Growth DataFetal Growth Data

Location/date characteristics Number of subjects

Lubchenco Denver 1958-61 High altitude, white/hispanic, Low SEC

5635

Fenton 3 IU data sets * Kramer * Niklasson * BeebyCDC data.

Olsen 33 US states 1998-2006

Racially diverse 257,855

Fenton Chart

Data Sets: Kramer et al: 676,605 infants 22-43 weeks Nicholson et al : 376,000 Swedish infants

28-40 weeks Breeby et al: OFC (N=29090) and Length

(N=26,973) 22-40 weeks CDC Data

Time period 1963-2001

Postnatal Growth Charts

Accounts for initial weight loss Dancis: Data 1948, very small

sample size in lowest weight group Ehrenkranz: Pediatrics 1999:104:280

N=1660 14-16 g/kg/d weight gain 0.9 cm/week increase length 0.35 cm/week increase OFC

Infant Growth References

A variety of growth references were developed and and used

in the U.S. since the early 1900’s

Growth references: timeline Stuart/Meredith Growth

Charts (1946-76) Caucasian, Boston/Iowa

city, small sample size NCHS growth charts (1976-

1978) Cross sectional Data from

NHES, NHANES, and FELs CDC produced normalized

version 1978 WHO recommended

international use

CDC (2000) 5 cross sectional nationally

representative surveys between 1963-1995

Included more breast fed infants

WHO (2006) Data from Brazil, Ghana,

India, Norway, Oman and USA

Multiethnic, affluent Exclusive breastfeeding to 4

months Solids according to

recommendations 6 months Continued breastfeeding to

12 months

Growth Charts

CDC/NCHS http://www.cdc.gov/growthcharts/

World Health Organization http://www.who.int/childgrowth/en

NCHS growth charts: Concerns Infant data: Fels study

Primarily formula fed Underrepresented groups: largely

caucasian, middle class Intervals of measurements (q3

months from 3-36 months) may not define dynamic patterns during rapid growth phases

Statistical smoothing proceedures

CDC Growth Charts (compared to older NCHS

Standardized data collection methods

Expanded sample More breastfed infants Exclusions

VLBW infants NHANES III weight data for >6 year

olds

CDC/NCHS Growth Charts

Clinical charts for infancy for girls and boys: weight length weight for length OFC

Choice between outer limits at 3rd and 97th or 5th and 95th percentiles

WHO Child Growth Standards

Released new growth standards April 2006 Assumed that infants and children

between birth and 5 years grow similarly when needs are met.

Concerns for CDC charts included: Frequency of growth measures during

dynamic periods of infant growth Statistical methods

Standard vs Reference Released new growth

standards April 2006 Assumed infants and

children grow similarly when needs are met.

Concerns for CDC charts included:

Frequency of growth measures during dynamic periods of infant growth

WHO growth charts

Full term low birthweight infants not excluded

Birth to 2 years N 1743 ----- 882

2-5 years N 6669

WHO v.s. CDC

Infancy WHO mean > CDC mean birth-6

months “healthy breastfed infants track

weight/age along WHO but falter on CDC”

Cross at 6 months and WHO mean < 6months

WHO v.s. CDC CDC

Heavier, shorter WHO

taller WHO

Higher estimates of overweight Lower estimates of underweight,

undernutrition

CDC Recommends use of WHO growth standard

2006 convened expert panel of NIH and AAP to review scientific evidence and use of WHO growth charts in clinical US settting

September 2010 recommended use of WHO charts for infants birth to 2 years

CDC Recommendations for infant growth charts http://www.cdc.gov/growthcharts Use WHO charts from birth-24 months CDC charts for > 24 months As a screen, 3rd and 97th percentile on

WHO corresponds to 5th-95th on CDC Clinicians should be aware that fewer

individuals will be screened as “underweight” and more as “overweight” using WHO

Controversies/Issues Screen vs assessment Standard vs reference Typical vs ideal growth Environmental influence Variety of diets may result in acceptable

growth and nutrition status Normal population divesity Plot individuals on both CDC and WHO.

Does your assement change? Absolute size vs pattern

Alterations in Growth

SGA LGA Preterm birth Failure to grow (FTG)

SGA Infant < 10th percentile

Symmetric vs asymmetric

Not a part of natural diversity or genetically determined

Placental insufficiency limiting nutrient supply to fetus

SGA Infant Etiology Programing Timing Body

Composition Cell number Cell size LBM vs. adiposity BMC

Increased BMR Impaired

gluconeogenesis Risk for

hypoglycemia Risk for iron

deficiency anemia Risk for adult

onset diseases

LGA Infant > 90th percentile Not part of

natural diversity or genetically determined

Macrosomic, increased adiposity vs proportionate

Preterm Birth

Extra uterine Growth Restriction

Extra uterine growth restriction refers to the development of severe nutrient deficits in premature infants during hospitalization

Extra uterine Growth restriction Remains a Serious Problem in Prematurely Born Neonates

Cooke et al Arch Dis Childhood 2004:89:428-430

N= 659 from 4 level III and 10 level I-II units Variable but universal incidence of postnatal growth

retardation (PGR) comparing level III and level I-II units PGR in level III associated with birth weight, birth weight Z

score, and GA 45% of PGR in level III unit unexplained (? Variability in

nutritional practices) ? PGR in level I-II vs. level III

Extra uterine Growth restriction Remains a Serious Problem in Prematurely Born Neonates

Clark: Pediatr 2003 N=24,371 from 124 NICUs 1997-2000 Estimated based on growth <10th percentile at

discharge Estimates:

Wt: 28% Lngth: 34% OFC: 16%

Extra uterine Growth Restriction

NICHD Neonatal morbidity Research network 16% ELBW infants are SGA at birth At 36 weeks CA 89% demonstrate

growth failure Follow up at 18-22 months show 40%

with weight, length, OFC <10%

Development

In utero

Fetal GI tract is exposed to constant passage of fluid that contains a range of physiologically active factors: growth factors hormones enzymes immunoglobulins

These play a role in mucosal differentiation and GI development as well as development of swallowing and intestinal motility

At Birth

Gut of the newborn is faced with the formidable task of passing, digesting, and absorbing large quantities of intermittent boluses of milk

Comparable feeds per body weight for adults would be 15 to 20 L

Gastrointestinal Maturation

Reference Josef Neu, Gastrointestinal Maturation and

implications for infant feeding, Early Human Development 2007 83 (767-775)

Neonatal Gastroenterology, Clinics in Perinatology June 1996 23:2

Weaver and Lucas Development of Gastrointestinal Structure and Function, Chapter 3 in Neonatal Nutrition and Metabolism ed Hay Mosby 1991

Nutrition and Metabolism of the Micropremie in Clinics in Perinatology March 2000n 27:1

Gastrointestinal Maturation

Intestinal length increase 1000X from 5-40 weeks, doubles in the last 15 weeks.

Villi formed at 16 weeks Fetus begins to swallow around 16

weeks by 2nd trimester is swallowing as frequently as every 45 minutes. By term, the fetus ingests approximately 300 ml/d

GI development Weeks GA

Esophagus Superficial glandsSquamous cells

2028

Stomach Gastric glandsPylorus and fundus defined

1414

Small intestine Crypt and villusLymph nodesPeptides and hormonesNeurotransmittersMyenteric plexus

1414141214

Colon Diameter decreasesVilli disappear

2020

Pancreas Differentiation of exocrine and endocrine tissue

14

Liver Lobule formation 11

Maternal-fetal-placenta Interaction Individual metabolism

Glucose, amino acids, and fatty acids primary nutrients for tissue deposition and oxidative fuel

Hormonal regulation Not well understood Main hormones are placentally produced Insulin like growth factors induce cell proliferation and DNA,

increase glucose and amino acid uptake, and inhibit protein breakdown

Placental growth hormone stimulates IGF and is reduced in IUGR ? Leptin. Associated with fetal weight, fetal BMI, and fetal

fat mass

Carbohydrate Metabolism

Fetus Glucose and lactate

Glucose from maternal circulation via facilitated diffusion At birth, plasma glucose concentration about 2/3 maternal Used for oxidative fuel and source of carbon for glycogen

and other organic compounds Understress fetus can produce glucose with gluconeogenic

enzymes present at 10 weeks (but primarily maintained by maternal supply

hi

CHO: Term Infant

Enzyme origin substrate Activity in newborn

amylase Salivary glandsPancreasHuman milk

Starch/glucose polymers

ModerateAbsent<6moshigh

Glucoamylase Intestine Glucose polymers

high

Sucrase-isomaltase

Intestine High

Lactase Intestine Lactose high

CHO: Lactase

Lactase activity is highest in infancy (term) Term Infants

Lactase 30% of adult. Stimulated with first feeds

Preterm infants: Lactase levels remain low <36 weeks 30-40% NB levels Breath hydrogen tests confirm inefficient

digestion of lactose

CHO: Glucoamylase

Primarily responsible for starce digestion in youn infants (<3 months)

Glucoamylase activity increases during 3rd trimester

Adult levels reached by 12 months

CHO: Pancreatic Amylase

Pancreatic Amylase primarily responsible for complex starch digestion

Pancreatic amylase begins to increase after birth but may take up to 3 months before significant rise

Adult levels may not be reached until after 12 months of age

CHO

At birth Catoecholamines, thyroxin, and

glucagon increase and falling glucose levels stimulate glu-6-phosphatase

Glycogenolysis and hepatic glucose output are thus stimulated

Protein

Source of amino acids for protein synthesis

Release of bioactive peptides that contribute to regulation of many physiologic functions including metabolism, immunity, blood pressure, GI function, and food intake (eg CCK, GLP-1, glucagon, insulin)

Protein Metabolism

Fetus requires protein for protein synthesis and the provision of energy

Maternal-fetal amino acid transfer is a complex process involving several sodium dependent transfer proteins. Intracellular and extracellular sodium gradient provides driving force

Fetal amino acid profile differs from neonate

Protein

Elevated levels of amino acids and products of protein metabolism may exceed renal and hepatic capacity to excrete excess nitrogen with resulting acidosis, hyperammonemia, elevated BUN, diarhea.

Potential consequences: neurodevelopmental, stimulation of insulin and IGF-1, which can enhance growth, adipogenic activity and may be linked to later obesity

Protein

Digested in upper intestine via pancreatic proteases. Most of the brush border and cytosolic peptidases are well developed in the preterm infant and peptide transport system is efficient.

Macromolucules can be actively taken up by pinocytosis and preterm infants have demonstrated to capability to absorb lactoferrin. Preterm infants have increased intestinal permeability

Whey proteins induce fast but transient increase in plasma amino acids. Concentrations peak at 1-2 hours and return to baseline after 3-4 hours

Casein proteins are associated with slow gastric emptying, a slower and reduced rise in plasma amino acids and inhibit whole body protein breakdown

Lipid Metabolism

Fetus Fetus requires large amounts of lipids

particularly within developing nervous system (DHA, ARA)

Fetus acquires lipid via maternal placental transfer and capable of synthesizing cholesterol and fatty acids

Transfer impacted by maternal FA profile Dependent on maternal supply for EFA

Lipid:Term

Lipase Cofactors Substrate Contribution to fat digestion

Gastric lipase None TG Moderate to high

Pancreas Colipase and bile salts

TG low

Carboxylesterlipase

Bile salts TG Unknown to high

Pancreatic lipase

Phospholipids and TG

unknown

Milk bile salt dependent lipase

Bile salts TG Moderate to high

Preterm

Bile acids and lipases limited Approx 30% newborn levels 24-36

weeks

Renal

Limited ability to concentrate urine in first year due to immaturities of nephron and pituitary

Potential Renal solute load determined by nitrogenous end products of protein metabolism, sodium, potassium, phosphorus, and chloride.

Urine Concentrations

Most normal adults are able to achieve urine concentrations of 1300 to 1400 mOsm/l

Healthy newborns may be able to concentrate to 900-1100 mOsm/l, but isotonic urine of 280-310 mOsm/l is the goal

In most cases this is not a concern, but may become one if infant has fever, high environmental temperatures, or diarrhea

Postnatal Acquisition of Intestinal Microbiome Following birth the

sterile newborn GI tract colonized by environmental microorganisms

State of mutualism (microbiome) role in health, growth, development.

Postnatal Acquisition of Intestinal Microbiome Systemic and

mucosal immune fx of NB differs from adult

Fetal immune system evolved to avoid maternal rejection vs process pathogens

Microbiome

NB must undergo extensive postnatal development of which the acquisition of GI microbiome is major determinant of early immune system

Role of breastmilk: establishment of symbiotic core microbiome

Development of Infant Feeding Skills Birth

tongue is disproportionately large in comparison with the lower jaw: fills the oral cavity

lower jaw is moved back relative to the upper jaw, which protrudes over the lower by approximately 2 mm.

tongue tip lies between the upper and lower jaws.

"fat pad" in each of the cheeks: serves as prop for the muscles in the cheek, maintaining rigidity of the cheeks during suckling.

feeding pattern described as “suckling”

Developmental Changes Oral cavity enlarges and tongue fills up less Tongue grows differentially at the tip and

attains motility in the larger oral cavity. Elongated tongue can be protruded to receive

and pass solids between the gum pads and erupting teeth for mastication.

Mature feeding is characterized by separate

movements of the lip, tongue, and gum pads or teeth

Development Neurophysiologic

Homeostasis Attachment Separation and

individuation Oral Motor

Stages of Development

Homeostasis Attachment Separation and individuation

Stages

Age Development

1-3 months Homeostasis * State regulation* Neurophysiologic stability

2-6 months Attachment * “falling in love”* Affective engagement and interaction

6-36 months

Separation and individuation

* Differentiation* Behavioral organization and control

Feeding behavior of infants Gessell A, Ilg FL

Age Reflexes Oral, Fine, Gross Motor Development1-3months

Rooting and suckand swallowreflexes arepresent at birth

Head control is poorSecures milk with suckling pattern, the tongue projectingduring a swallowBy the end of the third month, head control is developed

4-6months

Rooting reflexfadesBite reflex fades

Changes from a suckling pattern to a mature suck withliquidsSucking strength increasesMunching pattern beginsGrasps with a palmer graspGrasps, brings objects to mouth and bites them

7-9months

Gag reflex is lessstrong as chewingof solids beginsand normal gag isdevelopingChoking reflexcan be inhibited

Munching movements begin when solid foods are eatenRotary chewing beginsSits aloneHas power of voluntary release and resecuralHolds bottle aloneDevelops an inferior pincer grasp

10-12months

Bites nipples, spoons, and crunchy foodsGrasps bottle and foods and brings them to the mouthCan drink from a cup that is heldTongue is used to lick food morsels off the lower lipFinger feeds with a refined pincer grasp

Infant feeding and Growth

Goals Expectations Considerations