双胎妊娠孕期体质量对血清高敏C反应蛋白与妊娠期糖尿病关联的影响：一项队列研究

目的: 探讨双胎妊娠孕妇孕早期血清高敏C反应蛋白(high sensitivity C-reaction protein，hsCRP)与妊娠期糖尿病(gestational diabetes mellitus, GDM)的关联，以及孕前体重指数(body mass index，BMI)和孕期增重情况对这一关联的影响。方法: 选取2017年3月至2020年12月在北京大学第三医院产科募集的孕前BMI ≥18.5 kg/m²的双胎孕妇，采用颗粒增强免疫透射比浊法检测孕早期血清hsCRP，前瞻性随访得到孕期增重和GDM的发生情况。采用Logistic回归分析hsCRP与GDM的关联效应，转换得到风险比(risk ratio, RR)，采用分层卡方检验、中介效应分析BMI、孕期增重情况对hsCRP与GDM关联的影响。结果: 570名双胎妊娠孕妇中，31.6%发生了GDM，26.1%孕前超重或肥胖，49.5%孕期增重超过推荐范围。调整混杂因素后，孕早期血清hsCRP中三分位和上三分位发生GDM的风险是下三分位的1.42倍(95%CI：1.02~1.89)和1.54倍(95%CI：1.12~2.02)，且呈线性趋势(P=0.022)。中介效应分析表明，孕前BMI对高水平hsCRP增加GDM风险的解释程度为23.84% (P < 0.001)，对两者的关联存在部分中介效应。联合hsCRP和孕期增重情况发现，孕期增重超过推荐范围且hsCRP较高水平(>1.21 mg/L)者发生GDM的风险是孕期增重在推荐范围内且hsCRP在下三分位者的2.31倍(P < 0.01)。结论: 孕早期高水平hsCRP显著增加双胎妊娠发生GDM的风险，hsCRP-GDM关联独立于孕期增重，且孕前BMI对hsCRP-GDM关联存在部分中介效应。双胎妊娠孕期管理要同时注重全身炎症反应和孕期体质量，以降低GDM发生风险。

Effects of gestational weight on the association between serum high sensitivity C reac-tion protein and gestational diabetes mellitus among twin gestations:A cohort study

Objective: To investigate the association between serum high sensitivity C-reaction protein (hsCRP) in early pregnancy and gestational diabetes mellitus (GDM) among twin pregnant women, and to explore the effects of the pre-pregnant body mass index (BMI) and gestational weight gain (GWG) status on such association. Methods: Twin pregnant women with pre-pregnant BMI greater than or equal to 18.5 kg/m² were recruited at Department of Obstetrics and Gynecology of Peking University Third Hospital from March 2017 to December 2020. Serum samples collected in early pregnancy were analyzed for hsCRP using particle-enhanced immunoturbidimetric method. In the following visits, the information about GWG and GDM were prospectively collected in every trimester. The association effect between hsCRP tertiles and GDM were estimated using Logistic regression, and further converted into risk ratio (RR). Cochran-Mantel-Haenszel test and mediation analysis were used to explore the effects of BMI and GWG status on the association. Results: Among the included 570 twin pregnant women, 31.6% deve-loped GDM, 26.1% were pre-pregnant overweight or obesity, and 49.5% with GWG out of referenced range. After adjustment for confounding factors, risk of developing GDM in twin gestations with the middle tertile and highest tertile of serum hsCRP in early pregnancy were 1.42 fold (95%CI: 1.02-1.89) and 1.54 fold (95%CI: 1.12-2.02), respectively, compared with the lowest tertile of serum hsCRP, and there existed significantly linear trend (P=0.022). Findings from mediation analysis illustrated that pre-pregnant BMI had partial mediating effect on the association, and BMI accounted for 23.84% (P < 0.001) of the increasing GDM risks with elevated hsCRP. Joint analysis with hsCRP and GWG found that those who were with GWG out of referenced range accompanied with the higher hsCRP tertiles (>1.21 mg/L) had significantly 2.31 fold increased risk according to those who were with GWG in the referenced range accompanied with the lowest hsCRP tertile (≤1.21 mg/L, P < 0.01). Conclusion: Elevated hsCRP in early pregnancy significantly increased GDM risk among twin pregnant women. The hsCRP-GDM association was dependent on GWG status, and pre-pregnant BMI had partial mediating effect on such association. It is suggested that twin pregnant women should consider systemic inflammation and gestational weight at the same time to reduce GDM risk.