**1.5.1 Cohort studies giving risk information**

In the MIDIA study parents were informed about that their child had the high-risk genotype for T1D (babies carrying HLA-DRB1\*03-DQA1\*05-DQB1\*02/ DRB1\*04:01-DQA1\*03- DQB1\*0302) or not. 2.1% of Norwegian newborns carry the high-risk genotype, and this group represents approximately 34% of future cases of T1D. Children with the high-risk genotype have 7% risk for getting T1D before 15 years of age and a lifetime risk at 20% (Rønningen et al., 1991; Undlien et al., 1997; Joner & Søvik, 1982, 1989; Mølbak et al., 1994).

Several other studies have used predictive genetic testing of newborns as a strategy to solve research questions about environmental factors contributing to T1D, including BABYDIAB in Germany (Ziegler et al.; 2011, Schatz et al.; 2000), DIPP in Finland (Kimpimaki et al.; 2001), PANDA in Florida (Carmichael et al., 2003, Krischer, 2007), DiPiS in Sweden (Lernmark et al., 2004), DAISY in Colorado (Rewers et al., 1996), and the multinational TEDDY study in the USA and Europe (Kiviniemi et al.; 2007, TEDDY study group; 2008). The main advantage for study participants identified as having increased risk for T1D is the possibility of early detection of the destruction of the insulin producing cells by autoantibodies, resulting in a milder disease onset having parents who are prepared in advance for the possibility of T1D onset, and therefore will handle the new life situation with a child with T1D better than other parents. In addition children with known increased genetic risk for T1D who also have developed autoantibodies will be the first to participate in intervention studies when possible preventive get available. However, there may be disadvantages of living with the knowledge of an increased susceptibility to a disease with no prevention. Thus, even though predictive testing is highly acknowledged as a valuable research method per se, the predictive testing has given rise to concerned debate.

#### **1.5.2 Particular aspects for the Norwegian MIDIA and MoBa studies**

With the widespread and increasing use of genetic tests, assessing the adverse effects of information about susceptibility genes for disease on the tested subject is important. The MIDIA study aimed to estimate the effect on maternal mental health from receiving genetic risk information about their newborns. Outcome measurements were maternal self-reported scores of anxiety and depression symptoms, satisfactory with life, self-esteem, and serious worry about their child. A number of previous studies (Hood et al., 2005; Johnson et al., 2004; Kerrush et al., 2007) have examined maternal reactions after being informed about their children having elevated genetic risk for T1D. None of these studies have shown a significant effect on symptoms of anxiety or other mental health disorders as result of the testing, though a few mothers did seem to react strongly. Previous studies were conducted in a setting in which the mothers were asked questions about it in connection with the genetic testing project. The MIDIA study was designed differently. When completing the questionnaire the mothers were not aware that their answers were going to be used for any particular comparisons, though they were rightfully informed that the personal data would be used for multiple research purposes. Thus, our results were not affected by reporting bias associated with maternal attitudes towards genetic risk information or other factors motivating to under- or over-report poor mental health. Since 50% of mothers who got their child tested for genetic high-risk for T1D also participated in the Norwegian Mother and Child Cohort (MoBa) study, all data used came from MoBa. In MoBa data was available both from the 30th week of pregnancy and when the child was 6 months of age. These data therefore permit to answer the main question to what extent receiving information about a young child having high risk for T1D changes maternal well being and health.
