First trimester metabolic syndrome insulin resistance index and offspring congenital heart disease risk: The mediating role of gestational diabetes mellitus.

Background: The purpose of this research was to investigate the association between the first trimester metabolic score for insulin resistance (METS-IR) index and offspring congenital heart disease (CHD), and to pay special attention to the mediating role of gestational diabetes mellitus (GDM).

Methods: A total of 21,401 women without pre-existing diabetes were enrolled in a prospective birth cohort study conducted in China. The participants were categorized into four groups based on their METS-IR index scores. Multivariate logistic regression models were used to assess the association between the first trimester METS-IR and CHD in their offspring. Mediation analysis was conducted to determine if GDM mediates this association.

Results: The increase in the METS-IR index in the first trimester was positively correlated with a significantly increased risk of CHD in offspring. Compared with the low METS-IR level group, the CHD risk in the high METS-IR group increased by 40 %. There was a positive linear dose-response relationship between METS-IR and CHD risk. Joint exposure to GDM and an elevated first-trimester METS-IR index significantly increased the risk of CHD in offspring, with evidence of a synergistic interaction on both multiplicative and additive scales. The estimated mediation proportion was 20.15 %.

Conclusions: The first-trimester METS-IR index was associated with an increased risk of CHD, and GDM partially mediated the association between the METS-IR index in the first trimester and CHD.