Expanded Newborn Screening: The Nutrition Perspective

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Expanded Newborn Screening The Nutrition
Perspective

• Nutrition 526
• November 5, 2008
• Beth Ogata, MS, RD
• bogata_at_u.washington.edu

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Nutrition Involvement in NBS

• Policy
• Diagnostic/coordination
• Clinical
• Community

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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 diphosphate-galactose-4-epimerase
  deficiency

Galactose-1-phosphate uridyl transferase (GALT)
deficiency
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Example infant with galactosemia
Treatment eliminate all galactose from diet

• Food labels
• milk, casein, milk solids, lactose, whey,
  hydrolyzed protein, lactalbumin, lactostearin,
  caseinate
• Medications (lactose is often an inactive
  ingredient)
• Dietary supplements
• Artificial sweeteners

• Primary source is milk (lactose galactose
  glucose)
• Secondary sources are legumes
• Minor? sources are fruits and vegetables

Monitoring galactose-1-phosphate levels lt3-4
mg/dl
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Example Infant with galactosemia
POLICY RD participated on State Advisory Board to
select disorders, including galactosemia

• CLINICAL MANAGEMENT
• RD provides nutrition care as member of the
  Biochemical Genetics Team
• Initiation of formula
• Guidelines for monitoring intake
• Plans for follow-up
• RD as case manager

DIAGNOSIS COOORDINATION Presumptive positive
? RD in contact with family and local providers
to discuss appropriate feeding practices and
arrange clinic appointment
COMMUNITY RD at local health department provides
ongoing education to family, local care providers
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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

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Nutrition and NBS Clinical Management PKU

• Phenylketonuria
• Phenylalanine hydroxylase
• Dihydropteridine reductase
• Biopterin synthetase
• Establish diagnosis
• Presumptive positive NBS results
• gt 3 mg/dL, gt24 hrs of age
• Differential diagnosis
• ?? serum phe, nl tyr
• r/o DHPR, biopterin defects

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Current Treatment Guidelines

• With effective NBS, children are identified by 7
  days of age
• Initiate treatment immediately
• Maintain phe levels 1-6 mg/dl (60-360 umol/L)
• Lifelong treatment

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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

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Clinical Management PKU

• Goals of Nutrition Therapy
• Normal growth rate
• Normal physical development
• Normal cognitive development
• Normal nutritional status

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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)
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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 0.91.8
  mg/dl
• Normal 0.9-1.8 mg/dl

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Goals of Nutrition Support for Phenylketonuria
(PKU)
Interpretation of phenylalanine levels 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
gt 20 mg/dl Very damaging
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Phe Levels from NBS to Tx
Equilibrium achieved by 14 days of age
Diagnostic levels
Blood levels every 2 days because of rapid growth
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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 requirement
• 250 mg/d

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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

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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

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Effect of a single amino acid deficiency on growth
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Food Choices for PKU
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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 gtgt1625 mg phe
Total Protein 32.5 grams (1625 mg phe) DRI
(protein) 13.5 grams (675 mg phe) Phe
requirement 250 mg
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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 gtgt1625 250 mg phe

• To meet 250 mg phe ? minus milk, tuna, cottage
  cheese
• Total Protein5.5 g
• Is this adequate protein to support growth?
• Is this adequate energy to support growth?
• What about adequacy of other nutrients?

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Tools of Management Low protein food products
Phe content of regular products Phe content of regular products Phe content of low protein 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 65 mg/5 crackers LP saltines 3 mg/5 crackers
Potatoes 145 mg/cup
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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

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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

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Effective Blood Level Management in Childhood
Blood levels once per month, or more frequently
if needed for good management
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PKU Management GuidelinesSelf-management Skills
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Goal of Lifetime Management of PKU

• To maintain metabolic balance while providing
  adequate nutrients and energy for normal physical
  and intellectual growth

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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 lt2 mg/dl
  prior to conception and during pregnancy

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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
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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

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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

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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

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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.

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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.

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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.

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Nutrition and NBS CommunityThe 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?

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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

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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?

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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
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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

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NBS and the CommunityWhat 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?

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Caveats to Ponder

• Is it really a disorder?
• What are we talking about?
• Is GA1 really so different than GA2?
• If were out of MSUD Analog, can we use MSUD
  Maxamaid?
• Screening vs. diagnosis
• Is it really PKU?

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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?

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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?

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Additional Information

• Washington State Newborn Screening
  http//www.doh.wa.gov/ehsph/phl/newborn/default.ht
  m
• 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)