Cui Jinhui, Jiang Hui, Huang Fei, Xie Mengjun, Cui Ziyi, Chen Xinyuan, OUYang Liping, Li Ping, Wang Yanling
Department of Obstetrics and Gynecology, Third Affiliated Hospital of Sun Yat-Sen University, No. 600, Tianhe Road, Guangzhou, 510630, China.
Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
BMC Pregnancy Childbirth. 2025 Jul 16;25(1):765. doi: 10.1186/s12884-025-07885-6.
Insulin resistance during pregnancy, while physiologically adaptive to enhance fetal nutrient supply, becomes pathological when excessive, contributing to low birth weight (LBW). The triglyceride-glucose (TyG) index, a biomarker of insulin resistance, predicts gestational complications, but its pathways to birth weight disparities remain unclear. This study investigates whether and to what extent first-trimester TyG index influences birth weight through preterm birth and gestational complications.
In this retrospective cohort study, 8,605 singleton pregnancies from a Chinese hospital (2015-2021) were analyzed. TyG index was calculated from first-trimester fasting glucose and triglycerides. Outcomes included gestational diabetes mellitus (GDM), hypertension, preeclampsia, preterm birth, LBW, macrosomia, and small/large-for-gestational-age (SGA/LGA). Logistic/multinomial regression assessed associations, followed by causal mediation analysis (R medflex package) to decompose direct/indirect effects. Models adjusted for maternal age, body mass index, education, parity, and diabetes family history.
A 1-standard deviation TyG index increase was associated with elevated risks of gestational complications (i.e., GDM, gestational hypertension, and preeclampsia). Higher TyG index level also showed positive associations with adverse birth outcomes: preterm birth (OR = 1.20, 95% CI: 1.08-1.34), LBW (OR = 1.11, 95% CI: 1.00-1.24), and LGA (OR = 1.12, 95% CI: 1.05-1.21), but not with macrosomia or SGA. Mediation analysis revealed that individual gestational complications mediated 17.7% (GDM), 11.1% (gestational hypertension), and 18.9% (preeclampsia) of the TyG-LBW association, with a joint mediation effect of 37.5%. Preterm birth alone mediated 89.0% of the TyG index-LBW association. When considering all mediators together (preterm birth and gestational complications), the joint natural indirect effect was 1.12 (95% CI 1.05-1.18) with a null natural direct effect being 1.00 (95% CI 0.90-1.11), indicating full mediation. These mediation patterns were primarily evident among women with normal pre-pregnancy weight. Quartile-based comparisons (4th vs. 1st ) yielded similar results.
Our findings highlight a significant association between the first-trimester TyG index and LBW with preterm birth emerging as the primary mediating pathway and gestational complications contributing partially to this relationship. Future research should explore whether interventions aimed at preventing preterm birth and gestational complications can mitigate the LBW risk.
孕期胰岛素抵抗在生理上是一种适应性反应，可增强胎儿营养供应，但过度时会导致病理状态，进而引发低出生体重（LBW）。甘油三酯-葡萄糖（TyG）指数作为胰岛素抵抗的生物标志物，可预测妊娠并发症，但其与出生体重差异之间的关联途径尚不清楚。本研究旨在探讨孕早期TyG指数是否以及在多大程度上通过早产和妊娠并发症影响出生体重。
在这项回顾性队列研究中，分析了一家中国医院（2015 - 2021年）的8605例单胎妊娠。根据孕早期空腹血糖和甘油三酯计算TyG指数。研究结果包括妊娠期糖尿病（GDM）、高血压、先兆子痫、早产、低出生体重、巨大儿以及小于/大于胎龄儿（SGA/LGA）。采用逻辑/多项回归评估关联，随后进行因果中介分析（R medflex软件包）以分解直接/间接效应。模型对产妇年龄、体重指数、教育程度、产次和糖尿病家族史进行了校正。
TyG指数每增加1个标准差，妊娠并发症（即GDM、妊娠高血压和先兆子痫）的风险升高。较高的TyG指数水平还与不良出生结局呈正相关：早产（OR = 1.20，95% CI：1.08 - 1.34）、低出生体重（OR = 1.11，95% CI：1.00 - 1.24）和大于胎龄儿（OR = 1.12，95% CI：1.05 - 1.21），但与巨大儿或小于胎龄儿无关。中介分析显示，个体妊娠并发症介导了TyG与低出生体重关联的17.7%（GDM）、11.1%（妊娠高血压）和18.9%（先兆子痫），联合中介效应为37.5%。单独早产介导了TyG指数与低出生体重关联的89.0%。当综合考虑所有中介因素（早产和妊娠并发症）时，联合自然间接效应为1.12（95% CI 1.05 - 1.18），自然直接效应为1.00（95% CI 0.90 - 1.11），表明完全中介。这些中介模式在孕前体重正常的女性中最为明显。基于四分位数的比较（第4四分位数与第1四分位数）得出了类似的结果。
我们的研究结果强调了孕早期TyG指数与低出生体重之间存在显著关联，早产是主要的中介途径，妊娠并发症部分促成了这种关系。未来的研究应探讨旨在预防早产和妊娠并发症的干预措施是否可以降低低出生体重风险。
