Maternal antibody transfer confounds type 1 diabetes screening in infancy: results from the French TRAKR cohort - 15/10/26

Doi : 10.1016/j.diabet.2026.101797

Sarvenaz Metghalchi ^a, Anna Jones ^a, Elise Bismuth ^b, Jean-Claude Carel ^b, Jacques Beltrand ^a,^c, Agnès Sola-Gazagnes ^d, Etienne Larger ^a,^d, Nathalie Morel ^e, Jean-François Gautier ^f, Jean-Pierre Riveline ^f, Catherine Petit ^g, Alfred Penfornis ^g, Nadine Lucidarme ^h, Emmanuel Cosson ^i,^j, Chloé Amouyal ^k, Jacques Lepercq ^l, François Goffinet ^l,^m, Nelly Briand ⁿ, Pierre-Yves Ancel ^m,ⁿ, Christian Boitard ^a,^d, Roberto Mallone ^a,^d,^⁎

TRAKR Study Group ^⁎
Members of the TRAKR Study Group are listed in the Appendix.

^a Paris Cité University, Cochin Institute, CNRS, INSERM, Paris, France

^b Assistance Publique–Hôpitaux de Paris, Robert Debré Hospital, Department of Pediatric Endocrinology, Paris, France

^c Assistance Publique–Hôpitaux de Paris, Necker Hospital, Department of Pediatric Endocrinology, Paris, France

^d Assistance Publique–Hôpitaux de Paris, Cochin Hospital, Department of Diabetology and Clinical Immunology, Paris, France

^e Paris Saclay University, CEA, INRAE, Département of Medicines and Healthcare Technologies, SPI, Gif-sur-Yvette, France

^f Assistance Publique–Hôpitaux de Paris, Lariboisière Hospital, Department of Diabetology, Paris, France

^g Centre Hospitalier Sud Francilien, Department of Diabetology, Corbeil-Essonnes, Université Paris Saclay, France

^h Assistance Publique–Hôpitaux de Paris, Jean Verdier Hospital, Department of Pediatrics, Bondy, France

ⁱ Assistance Publique–Hôpitaux de Paris, Avicenne Hospital, Department of Endocrinology-Diabetology-Nutrition, Sorbonne Paris Nord University, Sorbonne Paris Cité, CRNH-IdF, CSO Ile de France Nord, Bobigny, France

^j Sorbonne Paris Nord and Paris Cité University, INSERM, INRAE, CNAM, Center of Research in Epidemiology and StatisticS (CRESS), Nutritional Epidemiology Research Team (EREN), Bobigny, France

^k Assistance Publique–Hôpitaux de Paris, Pitié-Salpétrière Hospital, Department of Diabetology, Paris, France

^l Assistance Publique–Hôpitaux de Paris, Port Royal Hospital, Department of Obstetrics, Paris, France

^m Université Paris Cité and Université Sorbonne Paris Nord, INSERM, INRAE, Centre de Recherche Epidémiologie et StatistiqueS (CRESS), Obstetrical, Perinatal and Pediatric Life Course Epidemiology (OPPALE Team), Paris, France

ⁿ Assistance Publique–Hôpitaux de Paris, URC-CIC Paris Necker/Cochin, Paris, France

^⁎⁎ Corresponding author: Roberto Mallone, INSERM U1016 Cochin Institute, GH Cochin-Port Royal, 123 boulevard de Port Royal, F-75014 Paris, France. INSERM U1016 Cochin Institute GH Cochin-Port Royal 123 boulevard de Port Royal Paris F-75014 France

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Highlights

•	At 8 months of age, islet autoantibodies often reflect maternal antibody transfer.
•	Most antibody-positive infants shared antibody specificity with their mothers.
•	These antibodies usually disappear during follow-up.
•	Screening from age 2 years may reduce misclassification and unnecessary follow-up.

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Abstract

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.

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Keywords : First-degree relatives, INNODIA, Islet autoantibodies, Passive maternal antibody transfer, Screening, TRAKR