1. Newborn Screening the Role of Public Health Nutrition Kim DeDino MS, RD, LD, CSP Pediatric Dietitian Ohio Department of Health

2. Outline History and current status of newborn screening in the US What is an inborn error of metabolism and how is it treated Special look at PKU and MCADD Challenges in newborn screening follow up/treatment Looking forward

3. What is Newborn Screening? Infants are screened shortly after birth for a number of disorders that are difficult or impossible to detect clinically Heel Stick Hearing Screen Congenital Heart Screen Ultimate goal is to prevent death or disability through early detection and treatment of these disorders Newborn screening is more than just testing —it is an integrated system linking the babies, parents, hospitals & physicians with the health department and appropriate medical care

4. Newborn Screening Blood Spot After 24 hours of age, heel stick is conducted at the hospital or by the midwife if a home birth, sample is overnighted to the lab The lab runs the sample and determines if it is within normal limits or if there are any abnormal findings If a high level is found, the pediatrician on record and the birth hospital is immediately notified Child referred to specialized medical follow up—including metabolic RD

5. History of Newborn Screening Early 1960’s: Robert Guthrie discovered a way to test for phenylketonuria in infants, using whole blood on filter paper Late 1960’s: pilot program for PKU testing successful, States adopt PKU screening 1980s and 90s: States vary widely in the type and number of disorders that are screened 1999: AAP Newborn Screening Task Force formed

6. History of Newborn Screening Early 2000’s: Tandem Mass Spectrometry becomes used more widely in newborn screening programs, greatly expanding the number of tests that can be run using a small amount of blood 2002: MCHB commissioned the American College of Medical Genetics to review the effectiveness of newborn screening and provide recommendations for a uniform panel 2007 Newborn Screening Saves Lives Act 2012: Uniform panel contains 31 disorders

7. What makes a disorder eligible for screening? 1.The availability and characteristics of the screening test 2.The availability and complexity of diagnostic services 3.The availability and efficacy of treatments related to the conditions

8. Disorders Screened Metabolic Disorders Endocrine Disorders Hemoglobinopathies Others Biotinidase deficiency Critical congenital heart disease Cystic fibrosis Classic galactosemia Hearing loss Severe combined immune deficiency

9. Screening in the US In the US, 12,500 infants are diagnosed annually with one of the 29 core conditions on the panel (exempting CCHD and SCID) In 2009, the most commonly diagnosed conditions were: 1.Hearing Loss 2.Primary Congenital Hypothyroidism 3.Cystic Fibrosis 4.Sickle Cell Disease 5.Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) 6.Galactosemia (Classic and variant) 7.Phenylketonuria

10. Tandem Mass Spectrometry The use of MS/MS allows for screening of multiple metabolic disorders using a single analytical run MS/MS weighs molecules MS/MS can identify acylcarnitines and amino acids present in the newborn’s blood and can also measure how much of each is present Can identify high risk for amino acid disorders, fatty acid oxidation disorders, and organic acidemias

11. What is an inborn error of metabolism? Normal metabolism: enzyme Substrate  Product PAH Phenylalanine  Tyrosine Inborn error: damaged/missing enzyme Substrate  PAH Phenylalanine  tyrosine

12. The metabolic conditions Organic Acid Disorders Example: Isovaleric Acidemia (IVA) Amino Acid Disorders Example: Phenylketonuria (PKU) Fatty Acid Oxidation Disorders Example: Medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD)

13. Nutrition therapy Amino Acid Disorders/Organic Acid Disorders Medical foods/Special Formula Supplements (vitamins, specific a.a., carnitine, MCT oil) Low Protein specialty foods Fatty Acid Oxidation Disorders Providing adequate carbohydrate calories day and night (spares fatty acids form being used for energy) Prevention of fasting May require extremely low fat diet depending on disorder Coverage is a challenge!

14. What does that really mean? For organic acidemias and amino acid disorders: 10-20% of total protein comes from food and 80-90% of total protein comes from special medical formula (child). No meat, fish, eggs, dairy, nuts Very minimal (if any) regular breads and cereals Measured amounts of fruits, vegetables, and low pro foods For fatty acid oxidation disorders: Cornstarch therapy before bed and/or scheduled night time feeding Possible need for low fat diet of 10% of calories (depends on disorder)

15. A closer look at PKU Autosomal recessive disorder Mutation in the gene for the liver enzyme phenylalanine hydroxylase (PAH), which converts phenylalanine to tyrosine Diet consists of Phenylalanine-free medical food (formula) Measured amounts of breastmilk or formula for infants Measured amounts of fruits, vegetables, and limited grains Can benefit from specialty low protein foods No meat, dairy, fish, eggs, and extremely limited grains New medication introduced in 2007 (Kuvan) Treatment monitored by checking frequent blood phenylalanine levels

16. Evolution of treatment in PKU In the past, infants and children were taken off diet around age 5 due to the assumption that the brain was developed and was no longer affected by high phenylalanine levels These children grew up and the women became pregnant— delivered children with multiple issues (microcephaly, heart defects, etc.) Further research indicated older children and adults “off diet” experienced numerous issues (both physical and emotional) Now we recommend “Diet for Life”, but many adults struggle to get coverage of their medical foods or insurance for monitoring. Some states do not provide access to medical foods/formula for people over 21 years.

17. A closer look at MCADD Medium-chain acyl-coenzyme A dehydrogenase deficiency Disorder of fatty acid oxidation that impairs the body’s ability to break down medium chain fats into acetyl-CoA. Autosomal recessive disorder, 1 in 10,000 births Disorder does not present clinically until periods of fasting

18. Nutrition therapy Goal: avoid fasting Acute illness (even minor) is often the cause of metabolic decompensation Interventions during illness are critical—must provide sweetened fluids, or if needed IV dextrose and IV carnitine Must carry Emergency Letter, Medical alert bracelet, glucose source Typical Diet—heart healthy diet, some use supplemental L- carnitine Infants can have breastmilk or standard infant formula (limit MCT) Child—30% fat and avoid over feeding

19. Food/Formula Coverage Metabolic formulas are considered “Medical Foods” The term medical food, as defined in section 5(b) of the Orphan Drug Act (21 U.S.C. 360ee (b) (3)) is "a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.“ Insurance typically excludes coverage of “foods” or “nutrition supplements” Amino acids, vitamins, etc may not have NDC coding and are not classified as drugs—so may not make it on Medicaid/Medicare drug formularies

20. Food/Formula Coverage WIC, being a supplemental program, often can provide only a portion of the required medical food State Medicaid programs vary in their coverage of oral formulas. Most Medicare programs prohibit coverage of oral formulas. Most early treated patients do not require tube feedings. State metabolic formula programs exist, with varying age and income requirements. State insurance law mandates can help in some cases, however are not a panacea (ex: ERISA) http://www.ncsl.org/issues-research/health/medically- necessary-foods-and-formula-laws.aspx http://www.ncsl.org/issues-research/health/medically- necessary-foods-and-formula-laws.aspx

21. Medical Foods and the Affordable Care Act 2011—Institute of Medicine issued a report on essential benefits that should be included in the insurance exchanges Medical Foods and specialty low protein foods were not included, citing lack of evidence based medical practice At this time, there is no requirement for states to cover these lifesaving products Advocacy groups continue to work on this challenging problem

22. Financial burden of low pro diets Specialized PKU formula costs approx $6000 or more per year Other amino acid disorders have a greater cost $80000 per year and up Supplemental amino acids $120 per 30 day supply of tyrosine from Vitaflo USA Low protein foods vs. regular foods Low protein mac and cheese costs $8.99 per 7oz box Kraft macaroni and cheese costs $1.45 per 7 oz box Low protein baking mix costs $29.99 per 6lb box Bisquick baking mix costs $13.46 per 6lb box

23. Metabolic Disorders and Nutrition Programs WIC National School Lunch Program Early Intervention Medicaid

24. WIC Many recommendations for infants, children, and pregnant women with metabolic disorders differ from traditional WIC nutrition advice Should be off the bottle at 1 year of age Low fat milk should not be given to a child under 2 years old Young infants should breastfeed at will and on demand Versus It is important for your child to finish all of his metabolic formula each day, whether that be in a cup or a bottle I understand your child’s medical condition requires a very low fat diet and whole milk is not right for him. Follow your metabolic physician’s guidance on combining breastfeeding and metabolic formula Local WIC staff need to be aware of metabolic disorders and know how to work with the medical team caring for the child

25. WIC resources Ohio WIC worked with Ohio metabolic RDs to create education materials for use with children on low protein diets (amino acid disorders and organic acid disorders) Can be found at http://www.nal.usda.gov/wicworks/Sharing_Center/gallery/fa mily5.html http://www.nal.usda.gov/wicworks/Sharing_Center/gallery/fa mily5.html

26. National School Lunch Program Accommodating Children with Special Dietary Needs in the School Nutrition Programs http://www.fns.usda.gov/cnd/guidance/special_dietary_needs.pdf USDA regulations 7 CFR Part 15b require substitutions or modifications in school meals for children whose disabilities restrict their diets. A child with a disability must be provided substitutions in foods when that need is supported by a statement signed by a licensed physician. Other accommodations include access to a salad bar or the fruit and vegetable of the meal, access to refrigeration for medical formula, etc.

27. Other programs Early Intervention —RDs can provide education to EI home visitors regarding where to get information about metabolic disorders Medicaid —RDs should advocate for enteral policies that do not prohibit all oral formulas Title V –Title V RDs can work closely with the metabolic RDs to help follow these children in the community. In Ohio, our home visiting RDs work very closely with our metabolic teams and provide “eyes in the home”.

28. Challenges Formula and supplement coverage Contradictory public health policies, for ex: Newborn screening is important, yet follow up (formula) is not covered Not all medical professionals know about metabolic disorders and their treatment, for ex: OBs who are unaware of maternal PKU syndrome Families and privacy advocacy groups that have fears about genetic testing and are questioning NBS programs

29. Looking to the future HRSA sponsored long term follow up database Goal—to help standardize care Need to continue to build the infrastructure for long term follow up and treatment of NBS disorders (incl. access to medical foods, access to insurance for adults) Need to continue to educate health professionals regarding these disorders and the importance of collaborating with genetic specialists Need to educate families on the benefits of NBS to them and to society, address their fears about genetic testing

30. Resources Genetic Metabolic Dietitians International (GMDI) http://gmdi.org/ National Newborn Screening and Genetics Resource Center http://genes-r-us.uthscsa.edu/ HRSA Newborn Screening http://mchb.hrsa.gov/programs/newbornscreening/index.html

31. HRSA Regional Genetics and NBS Collaboratives

32. Thank you