Diabetes & metabolism · 2026
Maternal antibody transfer confounds type 1 diabetes screening in infancy: results from the French TRAKR cohort.
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Metghalchi Sarvenaz, Jones Anna, Bismuth Elise, Carel Jean-Claude, Beltrand Jacques, Sola-Gazagnes Agnès, Larger Etienne, Morel Nathalie, Gautier Jean-François, Riveline Jean-Pierre, Petit Catherine, Penfornis Alfred, Lucidarme Nadine, Cosson Emmanuel, Amouyal Chloé, Lepercq Jacques, Goffinet François, Briand Nelly, Ancel Pierre-Yves, Boitard Christian, Mallone Roberto, TRAKR Study Group
Аннотация
AIM: The optimal age to initiate islet autoantibody (IAb) screening in first-degree relatives of individuals with type 1 diabetes (T1D) remains uncertain. The TRAKR cohort prospectively characterized IAb patterns in newborns of parents with T1D to assess the interpretability of early-life screening.
METHODS: We analyzed 148 children with available follow-up. Child blood samples were collected at birth and at 8, 18, 30, and 42 months, and parental samples during pregnancy. Insulin (IAA), GAD (GADA), IA-2 (IA-2A), and ZnT8 (ZnT8A) IAbs were measured using bridging ELISAs. Child-mother IAb specificities and longitudinal trajectories were compared.
RESULTS: At 8 months, 28/138 children (20.3%) were IAb+, of whom 25/28 (89.3%) had a single IAb and 25/28 (89.3%) had a mother with T1D. Among 21 IAb+ children with maternal IAb results, 18 (85.7%) shared IAb specificity with their mother, predominantly GADA (15/18, 83.3%). All 9 children GADA+ at 8 months with follow-up had GADA+ mothers; 6 seroreverted by 18 months and 1 by 30 months. All 5 children IAA+ at 8 months with follow-up seroreverted by 18 months. Only one child, who seroconverted to IAA and GADA at 18 months, progressed to clinical Stage 3 at 30 months, without ketoacidosis.
CONCLUSION: IAb positivity at 8 months frequently reflects passive maternal antibody transfer rather than endogenous islet autoimmunity. Screening during the first year of life may therefore overestimate child autoimmunity and prompt unnecessary follow-up. Initiating screening at 2 years of age should reduce misclassification while retaining the opportunity to detect early childhood seroconversion.
METHODS: We analyzed 148 children with available follow-up. Child blood samples were collected at birth and at 8, 18, 30, and 42 months, and parental samples during pregnancy. Insulin (IAA), GAD (GADA), IA-2 (IA-2A), and ZnT8 (ZnT8A) IAbs were measured using bridging ELISAs. Child-mother IAb specificities and longitudinal trajectories were compared.
RESULTS: At 8 months, 28/138 children (20.3%) were IAb+, of whom 25/28 (89.3%) had a single IAb and 25/28 (89.3%) had a mother with T1D. Among 21 IAb+ children with maternal IAb results, 18 (85.7%) shared IAb specificity with their mother, predominantly GADA (15/18, 83.3%). All 9 children GADA+ at 8 months with follow-up had GADA+ mothers; 6 seroreverted by 18 months and 1 by 30 months. All 5 children IAA+ at 8 months with follow-up seroreverted by 18 months. Only one child, who seroconverted to IAA and GADA at 18 months, progressed to clinical Stage 3 at 30 months, without ketoacidosis.
CONCLUSION: IAb positivity at 8 months frequently reflects passive maternal antibody transfer rather than endogenous islet autoimmunity. Screening during the first year of life may therefore overestimate child autoimmunity and prompt unnecessary follow-up. Initiating screening at 2 years of age should reduce misclassification while retaining the opportunity to detect early childhood seroconversion.