Transcript Expanded Newborn Screening

Expanded Newborn Screening:
The Nutrition Perspective
Nutrition 526
November 5, 2008
Beth Ogata, MS, RD
[email protected]
Nutrition Involvement in NBS
 Policy
 Diagnostic/coordination
 Clinical
 Community
Example: infant with galactosemia

Symptoms in newborn, if
untreated
– Vomiting, diarrhea
– Hyperbilirubinemia, hepatic
dysfunction, hepatomegaly
– Renal tubular dysfunction
– Cataracts
– Encephalopathy
– E. coli septicemia result
– Death within 6 weeks, if
untreated

Also
– Duarte variant
– galactokinase deficiency
– uridine diphosphategalactose-4-epimerase
deficiency
Galactose-1-phosphate uridyl transferase
(GALT) deficiency
Example: infant with galactosemia
Treatment: eliminate all galactose from diet



Primary source is milk
(lactose= galactose +
glucose)
Secondary sources are
legumes
Minor? sources are
fruits and vegetables

Food labels
– milk, casein, milk solids,
lactose, whey, hydrolyzed
protein, lactalbumin,
lactostearin, caseinate



Medications
(lactose is
often an inactive ingredient)
Dietary supplements
Artificial sweeteners
Monitoring: galactose-1-phosphate levels <3-4 mg/dl
Example: Infant with galactosemia
POLICY
CLINICAL MANAGEMENT
RD participated on
State Advisory
Board to select
disorders,
including
galactosemia
RD provides nutrition care
as member of the
Biochemical Genetics Team:
•Initiation of formula
•Guidelines for monitoring
intake
•Plans for follow-up
DIAGNOSIS &
COOORDINATION
“Presumptive positive” 
RD in contact with family
and local providers to
discuss appropriate feeding
practices and arrange clinic
appointment
RD as case manager
COMMUNITY
RD at local health department
provides ongoing education to
family, local care providers
Nutrition and NBS: Policy

Screening process (disorders, procedures)
RD participated in Advisory Board meetings, providing
input about nutrition-related treatment

Services and reimbursement
Nutrition consultant to state CSHCN Program
RD provides input about relevant state Medicaid policies

Training and education
RD provides information about management of metabolic
disorders to local WIC agencies
Nutrition and NBS: Clinical
Management – PKU

Phenylketonuria
– Phenylalanine hydroxylase
– Dihydropteridine
reductase
– Biopterin synthetase

Establish diagnosis
– Presumptive positive
NBS results

> 3 mg/dL, >24 hrs of
age
– Differential diagnosis


 serum phe, nl tyr
r/o DHPR, biopterin
defects
Current Treatment Guidelines
 With
effective NBS, children are
identified by 7 days of age
 Initiate treatment immediately
 Maintain phe levels 1-6 mg/dl (60360 umol/L)
 Lifelong treatment
Outcome Expectations

With NBS and blood
phenylalanine levels
consistently in the
treatment range
– Normal IQ and physical
growth are expected

With delayed
diagnosis or
consistently elevated
blood levels
– IQ is diminished and
physical growth is
compromised
Clinical Management: PKU
Goals of Nutrition Therapy
 Normal growth rate
 Normal physical
development
 Normal cognitive
development
 Normal nutritional
status
Clinical Management: PKU

Correct substrate
imbalance
– Restrict
phenylalanine
intake to normalize
plasma
concentration

Supply product of
reaction
– Supplement
tyrosine to maintain
normal plasma
tyrosine levels
Phenylalanine -------------------//----------------------- Tyrosine
(substrate)
phenylalanine hydroxylase
(product)
Goals of Nutrition Support for
Phenylketonuria (PKU)
 Maintain
plasma phenylalanine (phe)
between 1-6 mg/dl
– Without PKU, phe ~ 1.0 mg/dl
 Maintain
plasma tyrosine (tyr)
between 0.9–1.8 mg/dl
– Normal = 0.9-1.8 mg/dl
Goals of Nutrition Support for
Phenylketonuria (PKU)
Interpretation of phenylalanine levels
~1 mg/dl
Normal
1-6 mg/dl
Excellent
6-10 mg/dl
Good
10-15 mg/dl
Caution
15-20 mg/dl
Dangerous
> 20 mg/dl
Very damaging
Phe Levels from NBS to Tx
Diagnostic levels
Blood levels every 2 days
because of rapid growth
Equilibrium achieved by
14 days of age
Adjustments necessary to maintain
“safe” blood phe levels
 Usual
intake of phe
– Newborn on formula
 20
oz x 22 mg phe/oz = 440 mg phe
– 1 yo child on “regular” diet
 30
g protein = 1500 mg phe (DRI = 13.5 g)
– 7 yo child on “regular” diet
 50
g protein = 2500 mg phe (DRI = 19 g)
 Phenylalanine
– 250 mg/d
requirement
Management Tools

Specialized formula
provides
–
–
–
–

80-90% energy intake
89-90 % protein intake
tyrosine supplements
no phenylalanine
Phenylalanine to meet
requirement from infant
formula or foods
Formula Composition

Regulated by FDA
– Renal solute load
– Carbohydrate
source
– Fat source
– Amino acid source
– Vitamin and mineral
content

Designated by
clinician
–
–
–
–
–
Protein/energy ratio
Specific amino acid
Fluid balance
Total protein
Total energy
Effect of a single amino acid
deficiency on growth
Food Choices for PKU
Sample Menu: ~1 year old
Food
Protein (g)
¼ cup Cheerios
0.8
½ banana
0.6
½ cup milk
4
2 graham crackers
2
32.5 grams
½ cup milk
4
¼ tuna sandwich
8
(1625 mg phe)
½ peach
0.6
2 saltines
0.6
¼ cup juice
0
½ cup milk
4
½ banana
0.6
¼ cup cottage cheese
7
¼ cup green beans
0.3
TOTAL
32.5
>>1625 mg phe
Total Protein:
DRI (protein):
13.5 grams
(~675 mg phe)
Phe requirement:
250 mg
Sample Menu: ~1 year old
Food
Protein (g)
¼ cup Cheerios
0.8
½ banana
0.6
½ cup milk
4
2 graham crackers
2
½ cup milk
4
¼ tuna sandwich
8
½ peach
0.6
2 saltines
0.6
¼ cup juice
0
½ cup milk
4
½ banana
0.6
¼ cup cottage cheese
7
¼ cup green beans
0.3
TOTAL
32.5 5.5 g protein
>>1625 250 mg phe
To meet 250 mg phe
 minus milk, tuna,
cottage cheese:
Total Protein:5.5 g
•Is this adequate
protein to support
growth?
•Is this adequate
energy to support
growth?
•What about
adequacy of other
nutrients?
Tools of Management: Low protein
food products
Phe content of regular
products
Phe content of low protein
products
Rice
300 mg/cup
LP rice
23 mg/cup
Pasta
163 mg/cup
LP pasta
5 mg/cup
Bread
105 mg/slice
LP bread
10 mg/slice
Cheerios 93 mg per ½ cup
LP Loops
5 mg per ½ cup
Saltines
LP saltines 3 mg/5 crackers
65 mg/5 crackers
Potatoes 145 mg/cup
Typical Food Pattern for a Child
with PKU
1 year old, weight & length at 50th %ile for age
Energy needs:
1000-1300 kcal
 Protein needs:
20 g
 Phenylalanine
needs: 250 mg


Formula
prescription:
– Phenyl-Free: 125 g
– Similac pdr: 50 g
– Water to 40 oz

Food prescription:
– 25 mg phe, 200
kcal, 0.5 g protein
Monitoring Adequacy of Treatment

Measure plasma amino acids
– Maintain in treatment range

Monitor nutrient intake
– Restrict phenylalanine, supplement tyrosine,
adequate protein, energy, other nutrients to
support growth and ensure good health

Monitor growth increments
– Typical growth expected

Monitor cognitive development
– Typical achievement expected
Effective Blood Level Management
in Childhood
Blood levels once per month, or more frequently if needed for good management
Age of Child
0-6 months
6 months
6-7 months
8-9 months
10-15 months
2-3 years
4-5 years
PKU
Management
Guidelines
Selfmanagement
Skills
5-6 years
7-10 years
10-12 years
13-14 years
15-17 years
18 years
Tasks for Children and Parents
Parents learn about and adjust to PKU
Start low-protein solid foods
Introduce cup
Introduce finger foods
Consider weaning from bottle (discuss transition with clinic staff)
Learn the concept of “formula first”
Learn to distinguish “yes” and “no” foods
Begin to learn to count foods – “how many”
Begin to use scale – “how much”
Assist in formula preparation
Teach children how to deal with other children’s curiosity about PKU
Prepare formula with decreasing supervision
Choose after school snack
Learn to pack school lunch
Begin to list foods on food record
Begin weighing food regularly on scale
Begin to prepare and consume formula independently each day (with
parental monitoring)
Prepare simple entrees independently
Know what blood levels are ideal
Increasing self-monitoring (with continued parent support) in formula
preparation and consumption
Independently manage total phenylalanine intake for the day
Learn menu planning
Responsible for food records
Responsible for all aspects of self-management
Able to do ‘finger poke’ for blood test
Able to explain basics of PKU – “What is it?”
Responsible for remembering recent blood levels
Continued parent support
Transition to adult-based clinic care
Ready to live independently, including:
-formula preparation and consumption
-food preparation and records
-monthly serum phenylalanine levels
Goal of Lifetime Management of
PKU
To maintain
metabolic balance
while providing
adequate nutrients
and energy for
normal physical and
intellectual growth
Maternal PKU Concerns/Outcomes

Women with PKU are at high risk for
delivering a damaged infant
– Placenta concentrates phe 2-4x
 Microcephaly
 Cardiac
problems
Infant IQ directly related to maternal
blood phe level
 Outcome improved with maternal blood
phe <2 mg/dl prior to conception and
during pregnancy

Nutrition and NBS: Community –
Glutaric Acidemia, type I


Defect in lysine and
tryptophan catabolism
Treatment:
– LYS- and TRP- restriction
(specialized formula, low
protein food pattern)
– Riboflavin
– Frequent monitoring
– Aggressively prevent
catabolism  metabolic crisis

Symptoms:
– Macrocephaly, frontotemporal
atrophy and delayed
myelination
– Myoclonic seizures, ataxia,
choreoathetosis
– Intermittent metabolic
acidosis
Glutaryl-CoA dehydrogenase deficiency
Example: Infant with GAI


12 month old
Medical conditions:
–
–
–
–


Glutaric acidemia, type 1 (identified by NBS)
Cystic fibrosis
Meconium ileus (repaired)
GER
Goals: optimal nutrition status, avoid metabolic
decompensation
Simplified nutrition-related history
– Breastmilk (or Isomil)+ Glutarex-1 to restrict lysine
– MCT oil, concentrated formula for weight gain; pancreatic
enzymes
– Solid foods introduced when developmentally appropriate
– NG tube  g-tube placed by 2 mo
Example: Infant with GAI
“The Players”

Family:
mother, father, infant,
extended family

Biochem team:
geneticist, nutritionist,
genetic counselor

Pulmonary team:
pulmonologist, nutritionist,
social worker, nurses

Primary care:
pediatrician

Community:
therapists, WIC nutritionist,
public health nurse, home
infusion company
Example: Infant with GAI
MNT and monitoring plan:
 Formula – preparation,
“recipe,” tolerance
 Blood levels – schedule,
lag between draw and
results
 Growth and nutrient needs
– balance approaches for
CF and GA1
 Food – introduction of
solids, oral aversion


Prioritization
Communication
Nutrition and NBS: Community
PHN and interpreter make monthly visits to
family of young child with MSUD.
Through pre-arranged phone calls, we can
discuss formula composition and
preparation, and solid foods.
This helps provide information between
regular clinic visits.
Nutrition and NBS: Community
A woman with PKU is enrolled in te First
Steps program (WA State MSS)
The RD with PKU Clinic provides consultation
to the First Steps RD, about management of
amino acid levels.
Nutrition and NBS: Community
The family of a child with propionic acidemia
receives formula from home infusion
company.
The home infusion RD is able to make home
visits to evaluate growth and intake, and
communicates with clinic RD.
This helps to ensure that the family is able
to implement recommendations.
Nutrition and NBS: Community
The baby has a “positive PKU test”
What were the blood phenylalanine (phe)
or other critical elevated blood levels?
 When was the sample collected?
 What is the protocol for confirming the
diagnosis?
 When was the diagnosis made?
 Did this referral come from a screening
test? If so, what is the next step toward
diagnosis?
 Is the family aware of the results?

Information Needed by Community and
Metabolic Teams Before MNT is Initiated
If an infant has been identified by NBS:
 Which NBS results are positive
 Birth date and age of the infant
 Birth weight and gestational age
 Current weight
 Current form of feeding, and intake
 Current health status of the infant
Critical Questions about Follow-up
and Coordination of Treatment






Who is your contact at the metabolic center?
What is the recommended treatment for the
disorder?
What nutrition intervention is required? How is
this monitored?
What is the mechanism for follow-up and testing?
Who will prescribe the specialized formulas?
How will the community and metabolic teams
communicate about intervention?
The Team
Child
Age-appropriate self-mgmt skills
Parents
Health status monitoring, teaching,
advocacy
Nutritionist
MNT, feeding skills
Geneticist
Medical monitoring
Lab
Laboratory monitoring
Medical Home
Well Child Care, family support
Psychologist
Developmental monitoring, screening
Community Providers
(RD, PHN)
Family support in community
School
Educational programs, tx monitoring
Therapists (OT, PT, SLP,
etc.)
Developmental monitoring and intervention
NBS and the Community:
Challenges
 Understand
the implications of the
results of newborn screening tests
 Develop a communication system
between the community providers
and the metabolic team for support
of treatment
 Interact with PCPs and families as
needed, to support appropriate MNT
NBS and the Community:
What you need to know
Which disorders are identified by NBS in
your state? Where do you find this
information?
 What is the difference between screening
and diagnostic results?
 What is the system for follow-up of
presumptive positive NBS results?
 How do you make referrals to regional
genetics clinics and specialty care clinics?

Caveats to Ponder
Is it really a disorder?
 What are we talking about?

– Is GA1 really so different than GA2?
– If we’re out of MSUD Analog, can we use
MSUD Maxamaid?
Screening vs. diagnosis
 Is it really PKU?

Scenes from the Annals of Reporting
and Acting on NBS Results
A primary care physician telephones are
reports there is a new baby with PKU and
asks that you please start the infant on
formula ASAP.
What additional information
do you need?
 What would you do?

Scenes from the Annals of Reporting
and Acting on NBS Results
You are on-call for the weekend for your
local hospital and you receive an order from
the newborn nursery on an infant with
presumptive galactosemia and a request for
the initiation of treatment.
What additional
information do you need?
 What would you do?

Additional Information



Washington State Newborn Screening
http://www.doh.wa.gov/ehsph/phl/newborn/default.htm
Star G-Screening, Technology, and Research in Genetics
http://newbornscreening.info
National Newborn Screening and Genetics Resource Center
http://genes-r-us.uthscsa.edu
Building Block for Life Volume 27, No 1. Pediatric Nutrition
Practice Group (Expanded NBS)
Building Block for Life Volume 30, No 3. Pediatric Nutrition
Practice Group (Genetics and Expanded NBS)