Serum triglyceride to high density lipoprotein cholesterol ratio in late pregnancy as a potential predictor of adverse birth outcomes: an analysis of real-world data

Abstract

Background: The association between serum triglyceride to high density lipoprotein cholesterol ratio (THR) in late pregnancy and adverse birth outcomes (ABO) remains controversial because of inconsistent results. The present study assessed the association between maternal serum THR and incidence of ABO [preterm birth (PTB), small and large for gestational age (SGA/LGA), low birth weight (LBW) and macrosomia] in a Chinese population.

Methods: A total of 11,553 consecutive participants from a real-world database with data on lipid profiles and birth outcomes were included. Logistic regression models were applied to assess the association between THR and incident ABO. Mediation analysis was performed to investigate the contribution of pregnancy complications [gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP) and pre-eclampsia (PE)] to this association.

Results: Approximately 6.6% (762/11,553), 8.9% (1023/11,553), 15.5% (1792/11,553), 4.3% (494/11,553), and 7.4% (851/11,553) of individuals developed PTB, SGA, LGA, LBW and macrosomia, respectively. Significant trends across the quintiles of THR toward decreasing incidence of SGA and LBW and increasing incidence of LGA and macrosomia were observed. The multivariate-adjusted odds ratios (OR) in the top quintile of serum THR (> 3.16) versus the bottom quintile (< 1.44) were 0.52 for PTB, 0.48 for SGA, 0.64 for LBW, 2.80 for LGA and 3.80 for macrosomia, respectively. A 1-standard deviation (SD) increase in serum THR was associated with decreased risk of PTB [OR = 0.84, 95% confidence interval (CI): 0.76-0.93), SGA (OR = 0.71, 95% CI:0.65-0.78) and LBW (OR = 0.76, 95% CI:0.65-0.90) and increased risk of LGA (OR = 1.40, 95% CI:1.32-1.49) and macrosomia (OR = 1.49, 95% CI:1.38-1.62). In mediation analyses, PE mediated - 19.8%, -10.6% and - 24.6% of THR-associated PTB, SGA and LBW, respectively, GDM accounted for - 3.7%, 6.8% and 4.3% of THR-associated PTB, LGA and macrosomia, respectively, and ICP explained - 1.9% and - 2.1% of THR-associated PTB and LBW, respectively. In addition, incorporating THR to ABO predictive models significantly improved the area under the curve for SGA (0.743 vs. 0.753, P < 0.001), LGA (0.734 vs. 0.745, P < 0.001) and macrosomia (0.786 vs. 0.800, P < 0.001).

Conclusion: Real-world data showed an association between serum THR in late pregnancy and ABO risk, and this association may be partially mediated by prevalent pregnancy complications (PE/GDM/ICP), suggesting a potential role of THR in predicting ABO (SGA/LGA/macrosomia).

Keywords: Adverse birth outcome; Large for gestational age; Macrosomia; Preterm birth; Small for gestational age; Triglyceride/HDL–C ratio.

Fig. 1

Serum triglyceride to HDL-C ratio among women who delivered PTB and FTB, SGA, AGA and LGA, and LBW, NBW and macrosomia (PTB/FTB: 2.26 ± 1.47 vs. 2.45 ± 1.39; SGA/AGA/LGA: 2.14 ± 1.17 vs. 2.38 ± 1.33 vs. 2.86 ± 1.72; LBW/NBW/macrosomia: 2.17 ± 1.28 vs. 2.40 ± 1.35 vs. 3.03 ± 1.77; all P < 0.001)

Fig. 2

Smooth curve fitting analysis of THR with ABO risk. Adjusted for age, BMI, parity, BP, gestational age (except for PTB), assisted reproduction, fetal sex and laboratory results (total protein, albumin, total bilirubin, direct bilirubin, ALT, AST, urea nitrogen, creatinine, total cholesterol, LDL-C and hsCRP)

Fig. 3

Serum triglyceride to HDL-C ratio in women with and with pregnancy complications (GDM/ICP/PE/PIH vs. NPC: 2.92 ± 1.76/2.74 ± 1.73/2.89 ± 1.45/2.60 ± 1.36 vs. 2.36 ± 1.34; all P < 0.001)

Fig. 4

ROC curves analysis to compare triglyceride, HDL-C, THR and the predictive models for ABO. Model 1 included age, BMI, parity, BP, gestational age (except for PTB), assisted reproduction, fetal sex and laboratory results (total protein, albumin, total bilirubin, direct bilirubin, ALT, AST, urea nitrogen, creatinine, hsCRP, total cholesterol, and LDL-C. Model 2, Model 1 plus THR