Happy Birthday, Early Check! One year ago this month, Early Check transitioned to screening babies for hundreds of serious health conditions using genome sequencing. To date, we've screened over 2000 babies using genome sequencing.

Type 1 Diabetes Risk Screening by Early Check

Type 1 Diabetes Risk Screening by Early Check

Early Check is a research study that offers free, voluntary screening for many health conditions not screened for by standard newborn screening. One of the conditions for which Early Check screens is type 1 diabetes (T1D). The Early Check screening identifies babies at higher risk for developing T1D in their lifetime so that they can be monitored more closely. Researchers and clinicians are still trying to determine the best way to identify children at higher risk for T1D.

Early Check is assessing the feasibility and acceptability of one population-based screening method. Below we address some common questions that may help you discuss this information with parents who have received an Early Check report for their baby.

Frequently Asked Questions

Type 1 diabetes is one of the most common chronic childhood conditions. Nearly 1 in 3 children with T1D present with diabetic ketoacidosis (DKA), which can be fatal.  Studies have shown that monitoring children at higher risk for developing T1D – before clinical onset of the condition - significantly reduces the risk of DKA.

Early Check uses DNA sequencing and calculation of a genetic risk score (GRS) to identify children who have a higher lifetime risk for T1D. We hypothesize that providing parents with a GRS, education, and appropriate screening will reduce lifetime risk of DKA for newborns in our study.

Families will receive results via a research report on the online Early Check portal. Results will fall within one of three risk categories:

  • low concern (less than 2% lifetime risk for T1D)
  • moderate concern (2-5% lifetime risk for T1D)
  • higher concern (greater than 5%-20% lifetime risk for T1D)
  • As a reference, the general population risk for T1D is 0.4%.

Follow-up

Low Concern

Moderate Concern

Higher Concern

 

Access to educational materials on T1D

X ​

X​

X​

Ability to contact the Early Check team at any time with questions or concerns

 

X

X

X

Genetic counseling session

​?

X​

X​

Islet autoantibody testing (9 months)

​Those with a first degree relative with T1D

X​

Positive Autoantibodies

Repeat islet autoantibody testing (12 months)

 

 

 

 

X

Inform pediatrician

 

 

X

Study visit with pediatric endocrinologist

 

 

X

A genetic risk score (GRS) is not diagnostic, rather it is a statistical calculation based on the presence or absence of multiple DNA variants, without taking environmental or other factors into account. In Early Check, the GRS provides a statistical prediction of lifetime risk to develop T1D.

Genetics only accounts for about half the risk for T1D. About 25% of children who will go on to develop T1D will get a low concern result on this test. The GRS (Sharp, 2019; Onengut-Gumuscu, 2019, Qu et al 2022) for T1D used by Early Check has been best studied and revised through several generations of improvement. These GRS scores have been independently validated (Tanagawa el al 2022; Prive et al 2022) in European and African descendent populations. The GRS scores have only had limited validation in other populations such as South and East Asians or Hispanic populations (Redondo et al 2022).  While DNA sequencing is highly accurate (> 99.5% per base), occasionally sequencing will yield missing data at some positions, which will reduce the accuracy of the GRS calculations.  

These symptoms can show up any time during childhood, but rarely in the first year of life: 

  • Frequent urination (persistent heavy diapers or go through multiple diapers a night)
  • Regression in potty-training or new bed-wetting
  • Extreme thirst 
  • Dry mouth
  • Increased appetite 
  • Failure to gain weight or weight loss
  • Rapid or heavy breathing
  • Fruity or sweet-smelling breath
  • Nausea or vomiting
  • Blurry vision

Islet autoantibodies are strongly associated with the development of T1D. A blood test can be done to look for islet autoantibodies to see if a child is developing T1D. Early Check offers this blood test for free to babies found to be at higher risk for T1D.

There is an FDA-approved treatment, Tzield (teplizumab), that can slow the progression of T1D in children ages 8 and above who have tested positive for 2 or more autoantibodies and have abnormal blood sugar levels. Otherwise, insulin is the mainstay treatment for clinically diagnosed T1D.

Low concern result

  • Evaluate the baby as you would all patients.
  • Do not discount symptoms of type 1 diabetes if they appear. Children with a low concern result can still develop T1D.
  • Reassure parents that there is nothing different they need to do in caring for their baby.
  • If there is a family history of T1D, the baby should still be considered at higher risk for T1D and counseled appropriately.

 

Moderate concern result

  • Evaluate the baby as you would all patients.
  • Reassure parents that there is nothing different they need to do in caring for their baby day to day. Parents should not change their baby’s diet due to these results.
  • Parents may be anxious about these results. Ask about parental wellbeing and refer for mental health support, as needed.
  • Counsel parents that most babies with a moderate concern result will not get T1D.
  • Educate parents on the symptoms of T1D and ask parents to contact you if symptoms appear.
  • Remind parents that monitoring their child’s health is normal and something they already do every day. If a child develops symptoms of other childhood illnesses, like a fever or rash, parents know to contact the pediatrician. Watching for symptoms of T1D is no different.
  • Islet autoantibody testing is offered by Early Check for babies with a moderate concern result plus a first degree relative with T1D. Early Check provides free autoantibody testing at 9 months of age for these children.
  • Children with a moderate concern result and no first degree relative with T1D will not be offered autoantibody testing through Early Check. If parents express anxiety about the results, or if you decide it is warranted, islet autoantibody testing may be considered. This test is available through LabCorp (test code) or for free as part of a separate research study called Autoimmunity Screening for Kids (ASK). Info For Parents | ASK Research Program | Denver (askhealth.org)
    • The optimal frequency of autoantibody testing remains unclear. Some T1D researchers suggest autoantibody testing at 2 years and again at 5-7 years (Sims, 2022; Besser, 2022).

 

Higher concern result

  • Evaluate the baby as you would all patients.
  • Reassure parents that there is nothing different they need to do in caring for their baby day to day. Parents should not change their baby’s diet due to these results.
  • Parents may be anxious about these results. Ask about parental wellbeing and refer for mental health support, as needed.
  • Counsel parents that even though babies with a higher concern result have an increased risk of developing T1D, most babies with this result will not get T1D.
  • Educate parents on the symptoms of T1D and ask parents to contact you if symptoms appear.
  • Remind parents that monitoring their child’s health is normal and something they already do every day. If a child develops symptoms of other childhood illnesses, like a fever or rash, parents know to contact the pediatrician. Watching for symptoms of T1D is no different.
  • Islet autoantibody testing is recommended by Early Check for babies with a higher concern result. Early Check provides free autoantibody testing at 9 months of age.
  • The optimal frequency of follow-up autoantibody testing remains unclear. Some T1D researchers suggest autoantibody testing at 2 years and again at 5-7 years (Sims, 2022; Besser, 2022). This test is available through LabCorp (test code) or for free as part of a separate research study called Autoimmunity Screening for Kids (ASK). Info For Parents | ASK Research Program | Denver (askhealth.org)
    • Nearly 100% of children with 2 or more positive autoantibodies will progress to T1D in their lifetime.
    • Approximately 15% of children with 1 positive autoantibody will progress to T1D.
    • Refer children with positive autoantibodies to pediatric endocrinology.

Please reach out to the Early Check team at support@earlycheck.org or 1-866-881-2715 if you have any questions about your patient’s results.

 

Published Clinical Guidelines

  1. Besser, R. E. J., Bell, K. J., Couper, J. J., Ziegler, A-G., Wherrett, D. K., Knip, M., …and Haller, M. J. (2022) ISPAD clinical practice consensus guidelines 2022: stages of type 1 diabetes in children and adolescents. Pediatr Diabetes, 23:1175-1187.
  2. Standards of Care in Diabetes – 2023, Volume 46 Issue Supplement_1 | Diabetes Care | American Diabetes Association (diabetesjournals.org)

References

  1. Besser, R. E. J., Bell, K. J., Couper, J. J., Ziegler, A-G., Wherrett, D. K., Knip, M., …and Haller, M. J. (2022) ISPAD clinical practice consensus guidelines 2022: stages of type 1 diabetes in children and adolescents. Pediatr Diabetes, 23:1175-1187.
  2. Onengut-Gumuscu, S., Chen, W-M., Robertson, C. C., Bonnie, J. K., Farber, E., Zhu, Z., …and Rich, S. S. (2019) Type 1 diabetes risk in African-ancestry participants and utility of an ancestry-specific genetic risk score. Diabetes Care, 42:406-415.
  3. Prive, F., Aschard, H., Carmi, S., Folkersen, L., Hoggart, C., O’Reilly, P. F., Viljalmsson, B. J. (2022) Portability of 245 polygenic scores when derived from the UK Biobank and applied to 9 ancestry groups from the same cohort. Am J Hum Genet., 109(1):12-23.