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Type 1 Diabetes-Related Antibodies in the Fetal Circulation: Prevalence and Influence on Cord Insulin and Birth Weight in Offspring of Mothers with Type 1 Diabetes

British Heart Foundation Cardiovascular Research Centre (R.S.L.), University of Glasgow, Western Infirmary, Glasgow G11 6NT, United Kingdom; Diabetes Research Institute and 3rd Medical Department (A.-G.Z.), Krankenhaus Munchen-Schwabing, Munich, Germany; University Department of Obstetrics and Gynaecology (B.A.H., A.A.C., F.D.J.), Centre for Reproductive Biology, University of Edinburgh, Edinburgh, United Kingdom; and Diabetic Department (J.D.W.), St John’s Hospital at Howden, West Lothian National Health Service Trust Livingston, West Lothian EH54 6PP, United Kingdom

Address all correspondence and requests for reprints to: Robert Lindsay, British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Western Infirmary, 44 Church Street, Glasgow G11 6NT, United Kingdom. E-mail: rsl3c{at}clinmed.gla.ac.uk.

During pregnancy, maternal type 1 diabetes-associated autoantibodies may cross the placenta. It is proposed that insulin antibodies (IA) allow transfer of insulin across the placenta, contributing to fetal hyperinsulinemia and macrosomia.

We assessed the prevalence of IA, the tyrosine phosphatase IA-2, and glutamic acid decarboxylase (GADA) in cord blood from offspring of mothers with type 1 diabetes (ODM, n = 138) and control mothers (control, n = 47) and further assessed cross-sectional relationships of antibody titers to birth weight and fetal insulin.

In ODM, antibodies were frequently present in cord blood; 124 ODM (95%) were positive for IA, 82 (59%) were positive for GADA antibodies, and 61 (44%) were positive for IA-2 antibodies. In controls, GADA and IA-2 antibodies were absent, whereas seven controls (15%) were positive for IA at low titers (P < 0.0001 ODM vs. controls for all).

ODM with IA (IA positive) or without IA (IA negative) had similar birth weights (mean ± SD: IA positive, 3.8 ± 0.7 kg; IA negative, 4.0 ± 0.6 kg; P = 0.31) and cord insulin concentrations (IA positive: median, 112 pmol/liter; interquartile range, 62–219 pmol/liter; IA negative: median, 114 pmol/liter; interquartile range, 59–194 pmol/liter; P = 0.96). Similarly, the presence of GADA and/or IA-2 autoantibodies (n = 103) was not associated with differences in birth weight or insulin concentrations. Antibody titers were not associated with birth weight or insulin as continuous variables in either controls or ODM.

Islet autoantibodies and IA are a common finding in cord blood of ODM, but we found no evidence that they influence offspring insulin concentrations or weight at birth.

This work was supported by Project Grant K/MRS/50/C2726 from the Chief Scientist Office of the Scottish Office.

Abbreviations: GADA, Glutamic acid decarboxylase; IA, insulin antibodies; IA-2A, antibodies to the tyrosine phosphatase IA-2; IQR, interquartile range; LMP, last menstrual period; ODM, offspring of mothers with type 1 diabetes.

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