Newborn Screening and Type 1 Diabetes: Historical Perspective and Current Activities at the CDC Division of Laboratory Sciences

Are free carnitine concentrations on newborn screening (NBS) 48–72 h after birth lower in patients who develop type 1 diabetes than in controls? A retrospective case-control study of patients with type 1 diabetes was conducted. NBS results of patients from a Sydney hospital were compared against matched controls from the same hospital (1:5). Multiple imputation was performed for estimating missing data (gestational age) using gender and birthweight. Conditional logistic regression was used to control for confounding and to generate parameter estimates (α = 0.05). The Hommel approach was used for post-hoc analyses. Results are reported as medians and interquartile ranges. A total of 159 patients were eligible (80 females). Antibodies were detectable in 86. Median age at diagnosis was 8 years. Free carnitine concentrations were lower in patients than controls (25.50 µmol/L;18.98–33.61 vs. 27.26; 21.22–34.86 respectively) (p = 0.018). Immunoreactive trypsinogen was higher in this group (20.24 µg/L;16.15–29–52 vs. 18.71; 13.96–26.92) (p = 0.045), which did not persist in the post-hoc analysis. Carnitine levels are lower and immunoreactive trypsinogen might be higher, within 2–3 days of birth and years before development of type 1 diabetes as compared to controls, although the differences were well within reference ranges and provide insight into the pathogenesis into neonatal onset of type 1 diabetes development rather than use as a diagnostic tool. Given trypsinogen’s use for evaluation of new-onset type 1 diabetes, larger studies are warranted.

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Development and Standardization of an Improved Type 1 Diabetes Genetic Risk Score for Use in Newborn Screening and Incident Diagnosis

Diabetes Care ◽

10.2337/dc18-1785 ◽

2019 ◽

Vol 42 (2) ◽

pp. 200-207 ◽

Cited By ~ 46

Author(s):

Seth A. Sharp ◽

Stephen S. Rich ◽

Andrew R. Wood ◽

Samuel E. Jones ◽

Robin N. Beaumont ◽

...

Keyword(s):

Type 1 Diabetes ◽

Newborn Screening ◽

Risk Score ◽

Genetic Risk ◽

Genetic Risk Score

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Screening for Type 1 Diabetes Risk in Newborns: The Freder1k Pilot Study in Saxony*

Hormone and Metabolic Research ◽

10.1055/s-0043-120921 ◽

2017 ◽

Vol 50 (01) ◽

pp. 44-49 ◽

Cited By ~ 7

Author(s):

Angela Hommel ◽

Florian Haupt ◽

Petrina Delivani ◽

Christiane Winkler ◽

Marina Stopsack ◽

...

Keyword(s):

Type 1 Diabetes ◽

Genetic Testing ◽

Pilot Study ◽

Newborn Screening ◽

Early Stage ◽

Diabetes Risk ◽

Screening Programs ◽

Increased Risk

AbstractAn increased risk for type 1 diabetes can be identified using genetic and immune markers. The Freder1k study introduces genetic testing for type 1 diabetes risk within the context of the newborn screening in order to identify newborns with a high risk to develop type 1 diabetes for follow-up testing of early stage type 1 diabetes and for primary prevention trials. Consent for research-based genetic testing of type 1 diabetes risk is obtained with newborn screening. Increased risk is assessed using three single nucleotide polymorphisms for HLA DRB1*03 (DR3), HLA DRB1*04 (DR4), HLA DQB1*0302 (DQ8) alleles, and defined as 1. an HLA DR3/DR4-DQ8 or DR4-DQ8/DR4-DQ8 genotype or 2. an HLA DR4-DQ8 haplotype and a first-degree family history of type 1 diabetes. Families of infants with increased risk are asked to participate in follow-up visits at infant age 6 months, 2 years, and 4 years for autoantibody testing and early diagnosis of type 1 diabetes. After 8 months, the screening rate has reached 181 per week, with 63% coverage of newborns within Freder1k-clinics and 24% of all registered births in Saxony. Of 4178 screened, 2.6% were identified to have an increased risk, and around 80% of eligible infants were recruited to follow-up. Psychological assessment of eligible families is ongoing with none of 31 families demonstrating signs of excessive burden associated with knowledge of type 1 diabetes risk. This pilot study has shown that it is feasible to perform genetic risk testing for childhood disease within the context of newborn screening programs.

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