Background: Higher maternal body mass index (BMI) and abnormal glucose metabolism during early pregnancy are associated with congenital heart defects in the offspring, but the exact mechanisms are unknown. Methods:We evaluated the association between maternal first trimester metabolic profile and transposition of the great arteries (TGA) in the offspring in a matched case-control study with 100 TGA mothers and 200 controls born in Finland during 2004-2014. Cases and controls were matched by birth year, child sex, and maternal age and BMI. Serum samples collected between 10and 14-weeks of gestation were analyzed for 73 metabolic measures. Condi-

Objective: To evaluate the association between maternal first trimester metabolic profile and transposition of the great arteries (TGA) in the offspring. Design: A matched case-control study using national register data and maternal first trimester blood samples. Settings: Finland Patients: A total of 100 mothers with TGA in their offspring and 200 controls matched by the year of birth and sex of the child, and the age and the body mass index (BMI) of the mother. Interventions: None. Main outcome measures: To identify the impact of 73 metabolic measure concentrations on the likelihood that a child would be born with TGA. Results: A higher concentration of four subtypes in extremely large very-low-density lipoprotein (VLDL) particles and one in large VLDL particles were observed in mothers with TGA in their offspring. This finding did not reach statistical significance after multiple testing correction. In the analysis of the subgroups of maternal BMI over 25 and 30 only, the odds ratios (OR) of the metabolic variables were higher compared to the original population. In the group with a BMI over 25 the mean OR was 1.3 (N= 111, total) and in the group with a BMI over 30 was 2.1 (N= 42, total). Conclusions: We found no statistically significant difference between the metabolic profiles of mothers with TGA in their offspring, and their controls. However, the trend in our BMI-matched study potentially indicates that the likelihood of TGA development associates with maternal early-pregnancy metabolic profile, and the association is more pronounced in the subgroups of BMI over 25 and 30. Further studies are needed especially in the higher BMI groups.