Pre-pregnancy BMI modifies the associations between triglyceride-glucose index in early pregnancy and adverse perinatal outcomes: a 5-year cohort study of 67,936 women in China

Abstract

Background: Triglyceride-glucose (TyG) index was suggested as a possible surrogate for insulin resistance and a predictor for cardiovascular diseases and diabetes in the non-pregnant population. However, the relationship between TyG index in early pregnancy and adverse pregnancy outcomes (APOs), and the contribution of pre-pregnancy body mass index (BMI) was still illusive.

Methods: A large retrospective cohort study involving 67,936 pregnant Chinese women between 2017 and 2022 was conducted. Data collection and laboratory tests were performed during the usual patient care. TyG index was calculated using ln [fasting plasma triglyceride (TG; mmol/L) × 88.5 × glucose (FPG; mmol/L) × 18.02/2]. Multivariable logistic regression models were applied to explore the relationship between TyG index and APOs. Interaction and stratification analyses were performed to assess the influence of pre-pregnancy BMI on the association. In addition, ROC curves were used to evaluate the potential predictive value of the TyG index and pre-pregnancy BMI.

Results: Positive associations between maternal early pregnancy TyG index and APOs, including gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), large for gestational age (LGA) and preterm birth (PTB) were demonstrated (all P < 0.001). Besides, there was a significant interaction effect of maternal pre-pregnancy BMI and TyG on the risk of GDM, HDP and LGA (P < 0.05). Women of pre-pregnancy overweight/obesity (OWO) with TyG index in the fourth quartile were at an increased risk for GDM [adjusted OR (aOR) and 95% CI, 3.82 (3.14-4.64)], HDP [aOR 95% CI, 1.34 (1.10-1.64)], for LGA [aOR 95% CI, 1.78 (1.44-2.19)], and PTB [aOR 95% CI, 1.53 (1.11-2.09)], compared with OWO mothers with TyG in the lowest quartile. In addition, the combination of BMI and TyG enhanced predictive performance for APOs, particularly in women with normal plasma TG and FPG levels.

Conclusions: Dose-response relationships were identified between elevated maternal TyG index in early pregnancy and APOs. A combination of early pregnancy TyG index and pre-pregnancy BMI may provide predictive value for APOs, even in low-risk women. Thus, early screening of fasting blood lipids and glucose simultaneously may be useful and convenient for the early identification of APOs, both among OWO and low-risk normal-weight women.

Keywords: Gestational diabetes mellitus; Hypertensive disorders of pregnancy; Large for gestational age; Pre-pregnancy BMI; Preterm birth; Triglyceride-glucose index.

Fig. 1

Association between Triglyceride-glucose index in early pregnancy the risk of adverse pregnancy outcomes. Multivariable logistic regression models with restricted cubic splines were applied to explore the dose–response relationship between maternal Triglyceride-glucose (TyG) index in early pregnancy and the risk of GDM (A), HDP (B), LGA (C) and PTB (D). These models were adjusted for maternal age, education, parity, and insurance status. BMI body mass index (calculated as weight in kilograms divided by height in meters squared), TyG Triglyceride-glucose, GDM gestational diabetes mellitus, HDP hypertensive disorders in pregnancy, LGA large for gestation age, PTB preterm birth

Fig. 2

Effect of triglyceride-glucose index in early pregnancy on pregnancy complications. Multivariable analysis was used to estimate the association of TyG in early pregnancy with risk of pregnancy complications and outcomes. All analyses were adjusted for age, education, parity, health insurance status, and pre-pregnancy BMI. TyG values in early pregnancy were divided into different quartiles (Q) categories. All analyses were adjusted for maternal age, education, parity, insurance status, and ALT level. Adjusted odds ratios (aOR) and risk differences of GDM, HDP, LGA and PTB for different TyG categories are calculated by comparing with the reference group (TyG < 25th). All risk differences, adjusted odds ratios, and the corresponding 95% CIs for each were calculated from the results of the multivariable model and adjusted for baseline risk imprecision. BMI body mass index, TyG Triglyceride-glucose, aOR adjusted odds ratios, Q quartiles, GDM gestational diabetes mellitus, HDP hypertensive disorders in pregnancy, LGA large for gestational age, PTB preterm birth

Fig. 3

The combined effect of early pregnancy FPG and pre-pregnancy BMI on pregnancy complications. Heatmap (filled contour plot) for the correlation of risk of pregnancy outcomes, including GDM (A), HDP (B), LGA (C), and PTB (D) according to the interaction of early-pregnancy FPG and pre-pregnancy BMI. Red indicates an increased risk of a pregnancy outcome, while blue indicates a decreased risk. The analysis was adjusted for maternal age, education, parity, and insurance status. BMI body mass index (calculated as weight in kilograms divided by height in meters squared), TyG Triglyceride-glucose, GDM gestational diabetes mellitus, HDP hypertensive disorders in pregnancy, LGA large for gestational age, PTB preterm birth, CI confidence intervals

Fig. 4

Predictive performance of the combined early-pregnancy TyG and pre-pregnancy BMI for pregnancy complications in the test cohort (N = 50,569). The enhanced predictive value of combining pre-pregnancy BMI and early-pregnancy TyG compared to their individual performance, with regards to GDM (A), HDP (B), LGA (C) and PTB (D), the receiver operating characteristic (ROC) curve evaluating the discriminative capabilities by calculating the AUC. TyG × BMI indicates the combined effect of TyG and BMI. AUC area under curve, CI confidence interval, BMI body mass index (calculated as weight in kilograms divided by height in meters squared), FPG fasting plasma glucose, TG triglyceride, TyG Triglyceride-glucose, BMI × TyG interaction term of pre-pregnancy BMI and TyG in early pregnancy, GDM gestational diabetes mellitus, HDP hypertensive disorders in pregnancy, LGA large for gestational age, PTB preterm birth