AIMS/HYPOTHESIS: Children with high-risk type 1 diabetes HLA genotype have increased risk of high relative birthweight (HrBW), while cord blood islet autoantibodies decrease the risk. As gestational infections may affect offspring type 1 diabetes risk, the aims were to test whether: (1) children of mothers reporting gestational infections have increased HrBW; (2) gestational infections explain islet autoantibody reduction of HrBW; and (3) gestational infections affect the association between HLA and HrBW. SUBJECTS AND METHODS: HLA genotypes and autoantibodies to glutamic acid decarboxylase, insulinoma-associated protein 2 and insulin were determined in cord blood of children born to non-diabetic mothers in the Diabetes Prediction in Skåne (DiPiS) study. Mothers reported gestational infections when the child was 2 months old. RESULTS: Fever or gastroenteritis during pregnancy was reported by 2,848/19,756 mothers (14%); 339 in more than one trimester. Children whose mothers reported infections had increased risk of HrBW (p = 0.0003), particularly in the absence of cord blood islet autoantibodies (interaction between HrBW, islet autoantibodies and infections, p = 0.0005). The effect on HrBW by high-risk HLA-DQ2/8 was aggravated by infections in more than one trimester (odds ratio [OR] = 5.24; p = 0.003) (interaction; p = 0.022). When infections were reported, cord blood islet autoantibodies decreased HrBW (OR = 0.34; p = 0.0002). CONCLUSIONS/ INTERPRETATION: This study revealed that: (1) gestational fever, gastroenteritis, or both, increased the risk of HrBW; (2) cord blood islet autoantibodies decreased the risk of HrBW only in combination with infections; and (3) infections aggravated the association between HLA-DQ2/8 and HrBW. These data suggest an interaction between HLA, gestational infections, islet autoantibodies and fetal growth.
AIMS/HYPOTHESIS: Children with high-risk type 1 diabetes HLA genotype have increased risk of high relative birthweight (HrBW), while cord blood islet autoantibodies decrease the risk. As gestational infections may affect offspring type 1 diabetes risk, the aims were to test whether: (1) children of mothers reporting gestational infections have increased HrBW; (2) gestational infections explain islet autoantibody reduction of HrBW; and (3) gestational infections affect the association between HLA and HrBW. SUBJECTS AND METHODS: HLA genotypes and autoantibodies to glutamic acid decarboxylase, insulinoma-associated protein 2 and insulin were determined in cord blood of children born to non-diabetic mothers in the Diabetes Prediction in Skåne (DiPiS) study. Mothers reported gestational infections when the child was 2 months old. RESULTS:Fever or gastroenteritis during pregnancy was reported by 2,848/19,756 mothers (14%); 339 in more than one trimester. Children whose mothers reported infections had increased risk of HrBW (p = 0.0003), particularly in the absence of cord blood islet autoantibodies (interaction between HrBW, islet autoantibodies and infections, p = 0.0005). The effect on HrBW by high-risk HLA-DQ2/8 was aggravated by infections in more than one trimester (odds ratio [OR] = 5.24; p = 0.003) (interaction; p = 0.022). When infections were reported, cord blood islet autoantibodies decreased HrBW (OR = 0.34; p = 0.0002). CONCLUSIONS/ INTERPRETATION: This study revealed that: (1) gestational fever, gastroenteritis, or both, increased the risk of HrBW; (2) cord blood islet autoantibodies decreased the risk of HrBW only in combination with infections; and (3) infections aggravated the association between HLA-DQ2/8 and HrBW. These data suggest an interaction between HLA, gestational infections, islet autoantibodies and fetal growth.
Authors: C S Hampe; L P Hammerle; L Bekris; E Ortqvist; I Kockum; O Rolandsson; M Landin-Olsson; C Törn; B Persson; A Lernmark Journal: J Clin Endocrinol Metab Date: 2000-12 Impact factor: 5.958
Authors: A Papadopoulou; K F Lynch; N Shaat; R Håkansson; S A Ivarsson; K Berntorp; C D Agardh; Å Lernmark Journal: Diabet Med Date: 2011-09 Impact factor: 4.359
Authors: H Elding Larsson; G Hansson; A Carlsson; E Cederwall; B Jonsson; B Jönsson; K Larsson; K Lynch; J Neiderud; A Lernmark; S-A Ivarsson Journal: Diabetologia Date: 2008-07-01 Impact factor: 10.122
Authors: Markus Lundgren; Åsa Sahlin; Camilla Svensson; Annelie Carlsson; Elisabeth Cedervall; Björn Jönsson; Ida Jönsson; Karin Larsson; Åke Lernmark; Jan Neiderud; Tore Vigård; Helena Elding Larsson Journal: Pediatr Diabetes Date: 2014-05-13 Impact factor: 4.866
Authors: Kristian F Lynch; Hye-Seung Lee; Carina Törn; Kendra Vehik; Jeffrey P Krischer; Helena Elding Larsson; Michael J Haller; William A Hagopian; Marian J Rewers; Jin-Xiong She; Olli G Simell; Jorma Toppari; Anette-G Ziegler; Beena Akolkar; Heikki Hyöty; Ezio Bonifacio; Åke Lernmark Journal: J Autoimmun Date: 2017-09-21 Impact factor: 14.511
Authors: A Carlsson; I Kockum; B Lindblad; L Engleson; A Nilsson; G Forsander; A-K Karlsson; A Kernell; J Ludvigsson; C Marcus; I Zachrisson; S-A Ivarsson; A Lernmark Journal: Int J Obes (Lond) Date: 2011-06-28 Impact factor: 5.095
Authors: Y Sterner; C Törn; H-S Lee; H Larsson; C Winkler; W McLeod; K Lynch; O Simell; A Ziegler; D Schatz; W Hagopian; M Rewers; J-X She; J P Krischer; B Akolkar; A Lernmark Journal: J Perinatol Date: 2011-04-28 Impact factor: 3.225