Preventing type 1 diabetes in childhood

Type 1 diabetes (T1D) is an autoimmune disease in which the insulin-producing β cells of the pancreas are destroyed by T lymphocytes. Recent studies have demonstrated that monitoring for pancreatic islet autoantibodies, combined with genetic risk assessment, can identify most children who will develop T1D when they still have sufficient β cell function to control glucose concentrations without the need for insulin. In addition, there has been recent success in secondary prevention using immunotherapy to delay the progression of preclinical disease, and primary prevention approaches to inhibiting the initiating autoimmune process have entered large-scale clinical trials. By changing the focus of T1D management from late diagnosis and insulin replacement to early diagnosis and β cell preservation, we can anticipate a future without the need for daily insulin injections for children with T1D

A comparison of UK preterm anthropometric charts and INTERGROWTH-21st: is it time to change growth charts?

Background: Current practice in the UK is to plot premature infant anthropometric measurements on Neonatal and Infant Close Monitoring (NICM) reference charts. These charts have several known limitations. The INTERGROWTH-21st Project has recently produced international ante- and postnatal growth standards. Exact knowledge of growth centiles allows clinicians to accurately assess infant nutritional requirements. Objective: To compare target centile measurements between INTERGROWTH-21st and UK NICM growth charts for premature infants. Method: Anthropometric measurements (weight and head circumference) of a convenience sample of neonates born between 24 and 32 weeks of gestation were analysed retrospectively. Measurements were collected across three time points and plotted on both the NICM and INTERGROWTH-21st growth charts. The respective centiles were compared and analysed by paired-sample t test, Wilcoxon rank test analysis, and multilevel mixed-effect linear regression models. Results: Centiles for weight and head circumference measurements of 96 infants plotted on INTERGROWTH-21st charts were significantly greater than their corresponding UK charts at all three time points. For weight, the average difference between the two charts varied from 9.1 to 16.4 centiles. The difference between the two charts was greater for female than male infants by up to 6.9 centiles (95% CI 10.1–3.8). Conclusion: Existing UK NICM reference charts are significantly different to the growth standards of INTERGROWTH-21st. The choice of which growth chart to adopt in the UK could have important consequences on premature infants’ future adult health and therefore requires further prospective observational studies with larger data sets including length measurements and more comprehensive population characteristics

A comparison of UK preterm anthropometric charts and INTERGROWTH-21st: is it time to change growth charts?

Background: Current practice in the UK is to plot premature infant anthropometric measurements on Neonatal and Infant Close Monitoring (NICM) reference charts. These charts have several known limitations. The INTERGROWTH-21st Project has recently produced international ante- and postnatal growth standards. Exact knowledge of growth centiles allows clinicians to accurately assess infant nutritional requirements. Objective: To compare target centile measurements between INTERGROWTH-21st and UK NICM growth charts for premature infants. Method: Anthropometric measurements (weight and head circumference) of a convenience sample of neonates born between 24 and 32 weeks of gestation were analysed retrospectively. Measurements were collected across three time points and plotted on both the NICM and INTERGROWTH-21st growth charts. The respective centiles were compared and analysed by paired-sample t test, Wilcoxon rank test analysis, and multilevel mixed-effect linear regression models. Results: Centiles for weight and head circumference measurements of 96 infants plotted on INTERGROWTH-21st charts were significantly greater than their corresponding UK charts at all three time points. For weight, the average difference between the two charts varied from 9.1 to 16.4 centiles. The difference between the two charts was greater for female than male infants by up to 6.9 centiles (95% CI 10.1–3.8). Conclusion: Existing UK NICM reference charts are significantly different to the growth standards of INTERGROWTH-21st. The choice of which growth chart to adopt in the UK could have important consequences on premature infants’ future adult health and therefore requires further prospective observational studies with larger data sets including length measurements and more comprehensive population characteristics

Successful integration of newborn genetic testing into UK routine screening using prospective consent to determine eligibility for clinical trials.

peer reviewedOBJECTIVE: INGR1D (INvestigating Genetic Risk for type 1 Diabetes) was a type 1 diabetes (T1D) genetic screening study established to identify participants for a primary prevention trial (POInT, Primary Oral Insulin Trial). METHODS: The majority of participants were recruited by research midwives in antenatal clinics from 18 weeks' gestation. Using the NHS Newborn Bloodspot Screening Programme (NBSP) infrastructure, participants enrolled in INGR1D had an extra sample taken from their day 5 bloodspot card sent for T1D genetic screening. Those at an increased risk of T1D were informed of the result, given education about T1D and the opportunity to take part in POInT. RESULTS: Between April 2018 and November 2020, 66% of women approached about INGR1D chose to participate. 15 660 babies were enrolled into INGR1D and 14 731 blood samples were processed. Of the processed samples, 157 (1%) had confirmed positive results, indicating an increased risk of T1D, of whom a third (n=49) enrolled into POInT (20 families were unable to participate in POInT due to COVID-19 lockdown restrictions). CONCLUSION: The use of prospective consent to perform personalised genetic testing on samples obtained through the routine NBSP represents a novel mechanism for clinical genetic research in the UK and provides a model for further population-based genetic studies in the newborn

Identification of infants with increased type 1 diabetes genetic risk for enrollment into Primary Prevention Trials-GPPAD-02 study design and first results

Primary prevention of type 1 diabetes (T1D) requires intervention in genetically at-risk infants. The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD) has established a screening program, GPPAD-02, that identifies infants with a genetic high risk of T1D, enrolls these into primary prevention trials, and follows the children for beta-cell autoantibodies and diabetes. Genetic testing is offered either at delivery, together with the regular newborn testing, or at a newborn health care visits before the age of 5 months in regions of Germany (Bavaria, Saxony, Lower Saxony), UK (Oxford), Poland (Warsaw), Belgium (Leuven), and Sweden (Region Skåne). Seven clinical centers will screen around 330 000 infants. Using a genetic score based on 46 T1D susceptibility single-nucleotide polymorphisms (SNPs) or three SNPS and a first-degree family history for T1D, infants with a high (>10%) genetic risk for developing multiple beta-cell autoantibodies by the age of 6 years are identified. Screening from October 2017 to December 2018 was performed in 50 669 infants. The prevalence of high genetic risk for T1D in these infants was 1.1%. Infants with high genetic risk for T1D are followed up and offered to participate in a randomized controlled trial aiming to prevent beta-cell autoimmunity and T1D by tolerance induction with oral insulin. The GPPAD-02 study provides a unique path to primary prevention of beta-cell autoimmunity in the general population. The eventual benefit to the community, if successful, will be a reduction in the number of children developing beta-cell autoimmunity and T1D.status: publishe