Participant characteristics stratified by quintiles of the serum THR are shown in Table 1. Among 11,553 included participants, 6946 (60.12%) were nulliparous, 2330 (20.2%) had prenatal BMI ≥ 30 kg/m2, and the median age at the time of admission for labor was 28 (IQR 26–31) years. The prevalence of PIH, PE, ICP and GDM were 2.1%, 3.5%, 6.2% and 8.4%, respectively. The ranges of THR for Q 1–5 was < 1.44, 1.44–1.88, 1.89–2.38, 2.39–3.16, and > 3.16, respectively. Higher THR was associated with older age, elevated prenatal BMI, higher assisted reproduction and cesarean section rate, increased gestational age and neonatal birth height and weight, elevated serum concentrations of total protein and triglyceride, and lower serum concentrations of total bilirubin, direct bilirubin, urea nitrogen, HDL-C, LDL-C and hsCRP. Moreover, pregnant women with higher THR had greater prevalence of PIH, PE, ICP and GDM (all P for trend < 0.001, Table 1). The baseline characteristics of the participants, categorized into PTB and full-term birth (FTB) groups, were also summarized in Table S1. Serum THR was positively correlated with maternal age (r = 0.085, P < 0.001), BMI (r = 0.132, P < 0.001), systolic BP (r = 0.019, P = 0.039), diastolic BP (r = 0.023, P = 0.015), fetal gestational weeks (r = 0.048, P < 0.001), birth length (r = 0.111, P < 0.001) and birthweight (r = 0.194, P < 0.001) and the levels of total protein (r = 0.109, P < 0.001) and triglyceride (r = 0.897, P < 0.001) and negatively correlated with the levels of total bilirubin (r=-0.079, P < 0.001), direct bilirubin(r=-0.127, P < 0.001), ALT (r=-0.021, P = 0.025), urea nitrogen (r=-0.029, P = 0.002), total cholesterol(r=-0.019, P = 0.042), LDL–C (r=-0.142, P < 0.001), HDL–C (r=-0.596, P < 0.001) and hsCRP level (r=-0.034, P < 0.001).
Table 1 Characteristics of the participants according to the THR quintiles (n = 11,553)Associations between serum THR and incident ABOThe median birth weight in the present study was 3,360 g with a proportion of 7.4% (854) macrosomia and 4.3% (494) LBW. Of the 11,553 neonates, 1,792 (15.5%) were classified as LGA, 1,023 (8.9%) as SGA and 762 (6.6%) as PTB. Table 2 indicated significant trends across the quintiles of THR toward decreasing incidence of SGA and LBW and increasing incidence of LGA and macrosomia (SGA and LBW: 13.0% and 6.9% in Q1, and decreased to 9.0% and 3.9%, 8.6% and 3.5%, 7.1% and 3.5%, and 6.5% and 3.5% in Q2, Q3, Q4, Q5, respectively; LGA and macrosomia: 8.6% and 3.0% in Q1, and increased to 12.9% and 5.2%, 16.4% and 7.7%, 17.4% and 8.6%, and 22.2% and 12.4 in Q2, Q3, Q4, Q5, respectively; all P for trend < 0.001). There were significant differences in serum THR among the participants who delivered PTB/FTB, SGA/AGA/LGA, and LBW/NBW/macrosomia newborns (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. 1). Significant differences in serum triglyceride and HDL-C concentrations were also observed among these participants (Fig S1 and Fig S2). In crude logistic regression analyses, both higher triglyceride and THR were associated with decreased risk of PTB, SGA, and LBW and increased risk of LGA and macrosomia, and these associations also persisted significantly after correcting for sociodemographic factors and laboratory findings, with the exception of LBW (Table 2 and Table S2). The multi variables-adjusted OR (95% CI) in the top quintile of THR (> 3.16) versus the bottom quintile (< 1.44) were 0.52 (0.41, 0.67) for PTB, 0.48 (0.38, 0.60) for SGA, 0.64 (0.41, 1.01) for LBW, 2.80 (2.31, 3.40) for LGA and 3.80 (2.85, 5.08) for macrosomia, respectively. In addition, higher HDL-C was associated with decreased risks of PTB, LGA, and macrosomia; the adjusted OR (95% CI) were 0.64 (0.45, 0.90), 0.72 (0.56, 0.91), and 0.64 (0.45, 0.90), respectively (Table S3). Each one standard deviation (SD) increment in serum THR was associated with 16%, 29%, and 24% decrease risk of PTB, SGA, and LBW and 40% and 49% increase risk of LGA and macrosomia, respectively. Similar results were observed in sensitivity analyses among individuals without advance age (Table S4), obesity (Table S5), multipara (Table S6) and PTB (for SGA/LGA/LBW/macrosomia, Table S7). In addition, multivariate-adjusted smooth curve fitting analyses indicated nonlinear associations of ABO with triglyceride, HDL-C and THR (Fig. 2. and Fig S3).
Table 2 Prospective association between the THR and ABO risk in the study populationFig. 1Serum 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. 2Smooth 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)
Mediation analysisSerum THR at the time of admission was significantly higher in women with pregnancy complications than those with non-pregnancy complications (NPC) (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. 3). In mediation analyses (Table 3), PE explained − 19.8%, -10.6% and − 24.6% of the association of THR with PTB, SGA and LBW, respectively. The proportions mediated by GDM were − 3.7%, 6.8% and 4.3% for the association of THR with PTB, LGA and macrosomia, respectively. ICP also had a slight mediating effect of THR on incident PTB and LBW (proportions mediated: -1.9% and − 2.1%, respectively).
Fig. 3Serum 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)
Table 3 Mediation analysis to investigate whether prevalent pregnancy complications mediated the association between THR and APO risk aPredicting ABO with THR and related modelsROC curves were constructed to evaluate sensitivity and specificity of triglycerides, HDL-C and THR separately in predicting ABO (Fig. 4). THR had shown better power in detecting SGA, LGA and macrosomia than using either triglycerides or HDL-C alone, which was determined by area under the curve (AUC) calculated in ROC analysis (SGA: 0.580 vs. 0.567/0.559; LGA: 0.604 vs. 0.587/0.582; macrosomia: 0.636 vs. 0.614/0.605; all P < 0.001, Table 4). The optimal THR cutoff values for detecting SGA, LGA, and macrosomia were 1.76, 2.13, and 2.14, respectively. To establish the predictive models of ABO at the time of admission, prenatal characteristics and laboratory findings were included. Compared with the models without THR, the addition of THR increased the AUC of SGA, LGA, and macrosomia from 0.743 to 0.753, 0.734 to 0.745, and 0.786 to 0.800, respectively (all P < 0.001, Table 4).
Fig. 4ROC 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
Table 4 Accuracy of triglyceride, HDL–C, THR and models to predict ABO
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