Developmental Perspectives on

Impact of Early Life Nutrition

Carmina Erdei, MD, FAAP

Neonatologist and Developmental-Behavioral Pediatrician
Brigham and Women’s Hospital, Boston, MA, USA
 I have no relationships
or conflicts of interest
to disclose

Learning objectives
1. Principles of early life nutrition
2. Growth and development in
preterm babies relative to
early life nutrition
3. Feeding as a neurodevelopmental
milestone

Early life nutrition

• Health benefits
• Neurodevelopmental benefits

“Good nutrition is the bedrock of child

survival, health and development.
Well-nourished children are better able
to grow and learn, to participate in and
contribute to their communities, and
to be resilient in the face of disease,
disasters, and other global crises”
 Nutritional shortages
during pregnancy and
in the early years may
promote obesity by
causing metabolic
changes in how energy
is used and stored

Chronic adult diseases are “programmed”

in utero by poor nutrition - Dr. David Barker

“Thrifty Phenotype”
 Food Insecurity,
Obesity & Development

Hunger-obesity paradox = unexpected relationship

food insufficiency ↔ childhood obesity

Food Insecurity,
Obesity & Development
Food insecurity in a child’s first years
➔ obesity at age 4
(Cook et al, Annals of the New York Academy of Sciences. 2008)

Reasons:
• Children to eat cheaper foods with‘empty calories’
• Tendency to overeat

Irregular eating patterns disrupt brain pathways

that control energy regulation and hunger signals
 Developmental Implications of
Childhood Obesity
• Weight bias/ stigmatization: employment, health care,
schools, media, and interpersonal relationships
• Overweight and obese youth outcomes:
• Teasing/ bullying
• Mental health problems: depression, anxiety,
low self-esteem, body dissatisfaction,
suicidal ideation
• Poor academic performance
• Lower physical activity
• Maladaptive eating behaviors

(Puhl et al, Best Pract Res Clin Endocrinol Metab. 2013)

Early Nutritional Status and

Later Risk
• Developmental programming: process by which an
insult has lasting effects on structure/function of the
developing organism

• Lifestyle factors influence risk for obesity, diabetes,

hypertension and dyslipidaemia

• Infant nutrition and a slower infant weight gain

pattern that matches metabolic needs ➔ protective
against later adult disease

(Singhal, Proc Nutr Soc. 2016)

 Early Life Nutrition

Breast = BEST

Safe alternatives to breastfeeding

• Nutritionally complete
• Key nutrients such as docosahexaenoic
acid (DHA), arachidonic acid (AA), lutein,
choline, folic acid, zinc

• Support optimal brain and body growth

and development

What is “good nutrition”?

• Human milk contains n-3 and n-6 LC-PUFA
(long chain polyunsaturated fatty acids)
• In a neonate, there is rapid accretion of
LC-PUFAs in whole body, brain and retina
• Advantages of breastfeeding:
• Visual acuity is better
• IQ a few points higher (still within average range)
• Lower risk for allergies/atopic disease
• Attachment, maternal mental health

(Fleith et al, Crit Rev Food Sci Nutr. 2005)

Breastfeeding and development

Breast milk promotes brain development,
particularly white matter growth
• 50 adolescents
• % expressed breast milk (EBM) in infant diet
• MRI scans at 15 -- > total, grey and white matter
volumes

• % EBM correlated significantly with verbal IQ

• In boys, % EBM correlated with all IQ scores, total

brain volume and white matter volume

(Isaacs et al, Pediatric Res. 2010)

 (Blencowe et al, 2013)

Long Term Outcomes in Preterms

1. Cognitive impairment
• Accounts for majority of functional disability at
school age
for each week < 33 weeks GA, mean IQ scores
decline 1.7 - 2.5 points
(Johnson et al, 2009; Kuban et al, 2016)

2. Neuropsychological impairments (~40%)

• Visual-motor integration
• Executive function
• Learning disabilities
• Language delays
(Marlow et al, 2007; Aarnoudse-Moens et al, 2009, Johnson et al, 2009)
 Long Term Outcomes in Preterms

3. Behavioral and emotional problems

• Behavioral problems in 20% of ELGANs at
6 years
• ADHD in 31% of survivors
(Bhutta et al, 2002; Samara et al, 2008)
• Internalizing conditions
(Botting et al, 1997, Indredavik et al 1994)
• Autism spectrum disorders 5 - 8%
(Limperopoulos et al, 2008; Hack et al, 2009; Kuban et al, 2009 and 2016)

What’s New in Preterm Nutrition?

Earlier, aggressive nutrient supply and
feeding regimes ➔ improvement in growth
and neurodevelopmental outcomes
• Trials looking at immunonutrients (bile salt-stimulated
lipase) and other bioactive peptides (lactoferrin) are
in progress
• Emerging data for importance of vitamin D for immune
regulation which plays a role in sepsis and gut function
• Early colostrum improves preterm immunity
• Potential role of macronutrient supply on other outcomes
(ROP)
• Attention to unique nutritional needs of late/ moderately
preterm infants
(Cleminson et al, 2016)

Early Life Nutrition in Preemies

LC-PUFAs
Advantages in preterm infants:
• Plasma and RBC FA status of infants fed for-
mulas with n-3 and n-6 LC-PUFA was closer to
the status of breast-fed infants than to that of
infants fed formulas containing no LC-PUFA
• Beneficial effects on visual acuity
• Improved visual attention and cognition
compared with infants fed formulas with
no LC-PUFA
(Fleith et al, Crit Rev Food Sci Nutr. 2005)
Long Term Developmental Studies

None of long-term follow-up studies

demonstrated beneficial effects of DHA/AA
supplementation on neurodevelopment

• Environmental factors that are

difficult to account for

• The choice of end-point measures

affects the outcomes

(Sun et al. J of Perinatol, 2016)

Principles of Early Life Nutrition

Some experts recommend
LC-PUFA intakes in the range
provided by feeding of human
milk typical of mothers in
Western countries

• AA to DHA ratio of approximately

1.5 and a DHA content up to 0.4%.

Preterm infants may benefit from slightly higher

levels of these fatty acids than term infants

(Fleith et al, Crit Rev Food Sci Nutr. 2005)

Questions

Paucity of data regarding direct relationship between

individual nutrients and milk additives and long term
neurodevelopmental outcomes

Donor breast milk is preferred by some institutions

as alternative to formula in term and preterm infants
• Potential immunologic benefits
• Slower rates of growth
• ? Neurodevelopmental benefits
 Better growth ➔ better
neurodevelopment?
• Cohort of 219 infants born < 1500g BW,
<30 weeks GA
• Follow-up at 5.4 years showed that infants with
better growth trajectories while in NICU showed:
• Reduced risk for an abnormal neurologic examination
• Reduced risk for impaired mobility
• Improved mental processing abilities

The effects of growth on neurodevelopment were

by far exceeded by the consequences of IVH
(Franz et al, Pediatrics. 2009)

Pattern
Improved growth in
perinatal period

Improved brain growth

Improved
neurodevelopment
Major Events in Brain Development
Term
Birth

Preterm Birth

4 8 12 16 20 24 28 32 36
Adulthood
Gestational Age (weeks)
Neurogenesis

Migration

Axonal/Dendritic Outgrowth

Synaptic Production

Myelination
Synaptic Elimination/Pruning

Adapted from Tau & Peterson, 2010;

Andersen 2003; Woodward, 2014.

Rapid, extensive cortical folding

in the NICU

27 weeks

30 weeks

34 weeks

Preterm at Term CGA Term

(38-40 weeks)

Hill et al. (2010)

Reproduced with permission from Dr. Terrie Inder, MD, PhD
Chair of Newborn Medicine , Brigham and Women’s Hospital

Brain Growth Predicts Neuro-

Development in Preterm Born Children

• 167 very preterm infants (< 30 weeks GA)

• severe cognitive delay – 17%, severe psychomotor
delay – 10%, cerebral palsy – 10%, neurosensory
impairment – 11%
• Brain MRI anomalies predict adverse outcomes
at 2 yrs
• cognitive delay (OR 3.6; 95 CI 1.5 - 8.7)
• motor delay (OR 10.3; 95 CI 3.5 - 30.8)
• cerebral palsy (OR 9.6; 95 CI 3.2 - 28.3)
• neurosensory impairment (OR 4.2; CI 1.6 - 11.3)

(Woodward et al, NEJM 2006)

 Brain Growth and Development
Predicts Neurodevelopment
in Preterms
Brain MRI abnormalities (particularly white matter
abnormalities) continue to predict neurodevelopmental
impairment at 4,6,9 and 12 years in very preterm

“The best way to

predict the future
is to create it.”
ABRAHAM LINCOLN

Growth & Development Practices

at BWH
Nutritional interventions

• Early introduction of breast

milk or donor milk feeds
• Gut priming
• Colostrum mouth care
• Early PN for infants < 1800g
• Protein 2.5-3 g/kg/day - DOL 0
• Intralipids 1-2 g/kg/day - DOL 0
 Growth & Development Practices
at BWH
Nutritional interventions

• Individualized nutritional plans for

each infant
• Increased caloric supplementation
after discharge with careful plan
for weaning calories during the
first few months

Growth and Development Unit at BWH

Developmental care
• Family centered care
• Breastfeeding
• “Skin-to-Skin”
• PT, OT, feeding therapy
• Reading to babies
• Music therapy
• “Cuddlers” program
• Child life support
• Term brain MRI for extremely preterms
• Parent mental health
Infant follow-up program (2017)

Growth and Development Unit (GDU) at

Brigham and Women’s Hospital, Boston, MA
 Family Centered Care
The best incubator is the family!

Parents and families

have a central role
in supporting their
baby’s health and
development

Patient and Family Centered Care

Provision of respectful, compassionate, culturally responsive

care that meets the needs, values, cultural backgrounds and
beliefs, and preferences of patients and their family
members by working collaboratively with them. It is grounded in
mutually beneficial partnerships among patients, families and
healthcare providers.

Families are members of the team, not simply objects of the

team’s attention. This requires a commitment to genuinely
work “with” patients and families, not just doing things
“to” or “for” them.

Changing the Paradigm for Neonatal Care

 Feeding Beyond Nutrition

Feeding Beyond Nutrition

• Infant oral feeding is

a neurodevelopmental
skill
• Each infant feeding
a social-emotional,
nurturing opportunity

Harry Harlow’s Love Experiment

 Feeding Disorders

A child’s refusal to eat certain food groups,

textures, solids or liquids (not due to
a traumatic event) for at least one month,
which causes them to not gain weight, not
grow well, or cause delays in development

Developmental Feeding
Disorders in Infancy
• Food refusal by the infant
in conflict with caregiver
• Inadequate weight gain ➔
failure to thrive
• Delay in language and
motor development
• Attachment problems

Feeding Difficulties in Preterm Infants

Prematurity

Morbidity Iatrogenic

Environment
Eating and drinking aren’t the body’s
first priority, breathing is

Transition to PO Feeding
in Preterms
Relative risk factors for delayed attainment
of full PO feeding:
BPD (RR=3.06, 1.36-6.89)
RDS (RR=1.63, 1.19-2.23)
PDA (RR=2.92, 1.20-4.05)
GERD (RR=1.38, 1.05-18.27)
SGA (RR=1.71, 1.15-2.56)
GA <28/40 (RR=2.63, 1.67-3.02)
(Howe et al, 2007; Eichenwald et al, 2001; Dodrill et al, 2008;
Bingham et al , 2010; Jadcherla et al, 2010; Buhler et al, 2004)

Feeding Interventions in
Preterm Infants
 POOR SSB
COORDINATION

INFANT TRIES INFANT CAN’T

CONTROL CONTROL
MILK FLOW MILK FLOW
Stop sucking
Slower sucking
Weaker sucking PROTECT AIRWAY
prolonged apnea

CAN’T PROTECT
AIRWAY
aspiration

POOR SSB
COORDINATION

INFANT TRIES INFANT CAN’T

CONTROL CONTROL
MILK FLOW MILK FLOW
Stop sucking
Slower sucking
Weaker sucking PROTECT AIRWAY
prolonged apnea

FEEDER HELPS CAN’T PROTECT

CONTROL AIRWAY
MILK FLOW aspiration
 FEEDER HELPS
CONTROL
MILK FLOW

THICKENED MODIFIED REDUCED VOLUME

FLUIDS UTENSILS &/OR DURATION
(e.g. slow flow nipple) OF FEEDS
(due to potential
risks of thickening
agents, we don’t MODIFIED SUPPLEMENTAL
use them with POSITIONING OR TOTAL
infants below (e.g. side-lying) TUBE FEEDING
term age)

MODIFIED
FEEDING STRATEGY
(e.g. external pacing)

Side-lying position for bottle feedings

Side-lying is the natural position that most
babies are held in for breastfeeding

SOFFI Model

• Infants achieved better physiological stability

and engagement during feeds
• Infants achieved full PO feedings in fewer days
• At follow-up, parents reported fewer feeding
problems
(Horner et al, 2014)
 SOFFI Model
Start with standard newborn bottle nipple and
hold the infant in a standard feeding position
(i.e. traditional cradle hold)
If problems ➔ implement compensations in this
order:
1. Slower flowing bottle nipple
2. Side-lying positioning
3. External pacing
(Ross et al, 2011; Philbin et al, 2011)

(BWH CPG,
Erdei & Dodrill, 2016)

Side-lying Positioning
LOW-RISK INFANTS HIGH-RISK INFANTS
Start with: Start with:
• Level 1 bottle nipple • Ultra Preemie bottle nipple
• Standard cradle hold • Side-lying position + horizontal milk flow
• External pacing

As needed (i.e. if the infant displays any decline in As able (i.e. provided infant is showing no decline in
physiological stability or engagement during PO physiological stability or engagement during PO
feeds) implement the following compensations, in feeds), consider trialing the following:
the following order, until a suitable option is found: • Remove external pacing
1. Slower flowing (therapeutic) bottle nipple • Transition to standard cradle hold
• Preemie (first) • Gradually increase flow
• Ultra Preemie (second) • Preemie nipple
2. Horizontal milk flow • Level 1 nipple
• Side-lying position OR
• Semi-upright position
• Avoid holding the infant in a reclined/ Note: All high-risk infants and any low-risk infants
supine position. requiring therapeutic bottle nipples should be seen
3. External pacing by the feeding therapist to determine support needs

BWH NICU data, 2015-2016

MBS 2016
n=43

No Aspiration Aspiration
6/43 (14%) 37/43 (86%)

Limited PO volume
NPO PO with compensations
(<10mL)
5/37 (14%) 20/37 (54%)
12/37 (32%)

BWH NICU data, 2015-2016

MBS 2016
n=43 Silent
Aspiration
35/37
(95%)
No Aspiration Aspiration
6/43 (14%) 37/43 (86%)

Limited PO volume
NPO PO with compensations
(<10mL)
5/37 (14%) 20/37 (54%)
12/37 (32%)
 MBS 2016 BWH NICU data, 2015-2016
n=43
Silent
Aspiration
35/37
No Aspiration Aspiration (95%)
6/43 (14%) 37/43 (86%)

Limited PO volume
NPO PO with compensations
(<10mL)
5/37 (14%) 20/37 (54%)
12/37 (32%)

Combination of 2 or 3 = 10/20 (50%)

Slower bottle nipple: 15/20 (75%)
Side-lying position: 4/20 (20%)
Thickened fluids: 11/20 (55%)

MBS 2016 BWH NICU data, 2015-2016

n=43
Silent
Aspiration
35/37
No Aspiration Aspiration (95%)
6/43 (14%) 37/43 (86%)

Limited PO volume
NPO PO with compensations
(<10mL)
5/37 (14%) 20/37 (54%)
12/37 (32%)

12 +20 = 32/37 (86%) Combination of 2 or 3 = 10/20 (50%)

Slower bottle nipple: 27/32 (84%)
Slower bottle nipple: 15/20 (75%)
Side-lying position: 7/32 (22%)
Side-lying position: 4/20 (20%)
Thickened fluids: 13/32 (41%)
Thickened fluids: 11/20 (55%)
Combination of 2 or 3 = 13/32 (41%)

Infant feeding is a complex nutritional,

physiologic and social-emotional experience.
Quality feeding experiences result in thriving
developing infants and foster improved
infant-caregiver relationships.
 Take-Home Points

Principles of early life nutrition – good nutrition

supports health and neurodevelopment

Growth and development in preterm babies is

related to the quality of early life nutrition

Physiologic and emotional aspects of feeding

impact growth, nutrition and child development