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体外受精治疗后口服葡萄糖耐量试验与围产期不良结局之间的剂量反应关联:一项基于双胎人群的队列研究。

Dose-response association between OGTT and adverse perinatal outcomes after IVF treatment: A cohort study based on a twin population.

作者信息

Tang Wei-Zhen, Huang Kang-Jin, Li Xia, Chen Ya, Wang Lan, Wang Ying-Xiong, Tang Yue, Deng Bo-Yuan, Liu Tai-Hang, Lan Xia

机构信息

Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Chongqing, 401147, China.

Department of Bioinformatics, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China.

出版信息

J Endocrinol Invest. 2025 Apr 19. doi: 10.1007/s40618-025-02585-6.

Abstract

BACKGROUND

Investigate the association between Oral Glucose Tolerance Test (OGTT) after in vitro fertilization (IVF) treatment and adverse maternal and neonatal outcomes in twin pregnancies.

METHODS

This retrospective study encompassed 2,541 twin pregnancies conceived through IVF treatment. Adverse maternal and neonatal outcomes were compared across different subgroups based on individual and combined OGTT classifications. A Spearman correlation regression model examined associations between OGTT levels at different time points and parameters such as gestational age, birth weight, and length. Subsequently, a Logistic regression model with restricted cubic splines (RCS) explored the relationships between OGTT levels at different time points and adverse pregnancy outcomes. Ultimately, nine types of machine learning models were developed using OGTT glucose values at different times to predict the risk of adverse pregnancy outcomes.

RESULTS

In subgroup analysis based on individual OGTT diagnosis, three time points were examined: fasting glucose (OGTT0), 1-hour post-glucose (OGTT1), and 2-hour post-glucose (OGTT2). OGTT0 ≥ 5.1 mmol/L was significantly associated with increased risks of ICP and neonatal hypoglycemia (p = 0.031; p = 0.022). OGTT1 ≥ 10 mmol/L correlated with higher risks of ICP and neonatal hyperbilirubinemia (p = 0.001; p = 0.002). OGTT2 ≥ 8.5 mmol/L was also linked to neonatal hyperbilirubinemia (p < 0.001). In combined impaired OGTT subgroups, the impaired fasting glucose (IFG) group had a higher incidence of neonatal hypoglycemia than the impaired glucose tolerance (IGT) group and IFG & IGT group, but a lower risk of neonatal hyperbilirubinemia. OGTT2 was negatively correlated with gestational age at delivery (β = - 0.08, p = 0.018), and both OGTT1 and OGTT2 were negatively correlated with neonatal birth weight (β = - 10.54, p = 0.008; β = - 15.04, p < 0.001), as well as OGTT2 with birth length (β = - 0.16, p = 0.009). The RCS logistic regression model indicated that the increase OGTT values was associated with the ICP risk, and the relationship between OGTT2 and neonatal hyperbilirubinemia was U-shaped. Among the various machine learning models predicting adverse outcomes, RandomForest exhibited superior performance.

CONCLUSION

OGTT values in twin pregnancies under IVF treatment are closely linked to adverse maternal and neonatal outcomes, with post-load glucose levels potentially serving as an early biomarker for identifying poorer outcomes. The inflection points in the RCS suggest a new indication point for the association between OGTT and adverse pregnancy outcomes in twin pregnancies conceived through IVF.

摘要

背景

研究体外受精(IVF)治疗后口服葡萄糖耐量试验(OGTT)与双胎妊娠中不良母婴结局之间的关联。

方法

这项回顾性研究纳入了2541例通过IVF治疗受孕的双胎妊娠。根据个体和联合OGTT分类,对不同亚组的不良母婴结局进行了比较。Spearman相关回归模型检验了不同时间点的OGTT水平与孕周、出生体重和身长等参数之间的关联。随后,采用带受限立方样条(RCS)的Logistic回归模型探讨不同时间点的OGTT水平与不良妊娠结局之间的关系。最终,利用不同时间的OGTT血糖值开发了九种机器学习模型,以预测不良妊娠结局的风险。

结果

在基于个体OGTT诊断的亚组分析中,检查了三个时间点:空腹血糖(OGTT0)、服糖后1小时(OGTT1)和服糖后2小时(OGTT2)。OGTT0≥5.1 mmol/L与ICP和新生儿低血糖风险增加显著相关(p = 0.031;p = 0.022)。OGTT1≥10 mmol/L与ICP和新生儿高胆红素血症风险较高相关(p = 0.001;p = 0.002)。OGTT2≥8.5 mmol/L也与新生儿高胆红素血症有关(p < 0.001)。在联合糖耐量受损亚组中,空腹血糖受损(IFG)组新生儿低血糖的发生率高于糖耐量受损(IGT)组和IFG&IGT组,但新生儿高胆红素血症的风险较低。OGTT2与分娩时的孕周呈负相关(β = -0.08,p = 0.018),OGTT1和OGTT2均与新生儿出生体重呈负相关(β = -10.54,p = 0.008;β = -15.04,p < 0.001),OGTT2与出生身长也呈负相关(β = -0.16,p = 0.009)。RCS逻辑回归模型表明,OGTT值的升高与ICP风险相关,OGTT2与新生儿高胆红素血症之间的关系呈U形。在预测不良结局的各种机器学习模型中,随机森林表现出卓越的性能。

结论

IVF治疗下双胎妊娠的OGTT值与不良母婴结局密切相关,负荷后血糖水平可能作为识别较差结局的早期生物标志物。RCS中的拐点为IVF受孕的双胎妊娠中OGTT与不良妊娠结局之间的关联提供了一个新的指示点。

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