Maternal smoking during pregnancy and offspring type 1 diabetes mellitus risk: accounting for HLA haplotype.

The main objective of this study was to investigate the risk of type 1 diabetes mellitus (T1D) in children exposed to tobacco smoking in utero, also taking genetic predisposition as expressed by HLA haplotype into account. In Skåne, the southernmost county of Sweden, all children born 1999-2005 who developed T1D were registered, resulting in 344 cases. For each child with T1D, three control children, matched for HLA haplotype and birthyear, were selected. Information on prenatal smoking exposure was retrieved from a regional birth register. Conditional logistic regressions were used to evaluate T1D risk following prenatal smoking exposure. In these data, maternal smoking in early pregnancy was associated with a higher risk of her child developing T1D [odds ratio (OR) 2.83; 95% confidence interval (CI) 1.67-4.80 for 1-9 cigarettes/day, and OR 3.91; 95% CI 1.22-12.51 for >9 cigarettes/day]. Results remained through all adjustments and sensitivity analyses. When genetic predisposition in terms of HLA haplotype was taken into account, we found that children exposed to smoking during fetal life were at higher risk of developing T1D in childhood.