Maternal first trimester metabolic profile in TGA pregnancies - a case-control study

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 the mean OR 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. What is already known on this topic? The most important structures of the heart develop during early pregnancy, but studies on the association of maternal metabolomics during the first trimester with CHD development are scarce. Maternal obesity and diabetes are known risk factors for CHD in the offspring but the precise developmental mechanisms underlying this risk remain unknown. What this study adds to this topic? The maternal metabolomic profile in early pregnancy is potentially associated with the likelihood of TGA development in the offspring. Metabolic markers in obese women may have a stronger association with the development of TGA but this connection requires further studies.