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北京大学学报（医学版） ›› 2022, Vol. 54 ›› Issue (3): 427-433. doi: 10.19723/j.issn.1671-167X.2022.03.006

• 论著 • 上一篇    下一篇

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

陈阳阳1,周玉博2,3,杨静4,花语蒙1,原鹏波4,刘爱萍1,*(),魏瑗4,*()   

  1. 1. 北京大学公共卫生学院社会医学与健康教育学系，北京 100191
    2. 北京大学生育健康研究所，国家卫生健康委员会生育健康重点实验室，北京 100191
    3. 北京大学公共卫生学院流行病与卫生统计学系，北京 100191
    4. 北京大学第三医院妇产科，北京 100191
  • 收稿日期:2022-01-27 出版日期:2022-06-18 发布日期:2022-06-14
  • 通讯作者: 刘爱萍,魏瑗 E-mail:apingliu@163.com;weiyuanbysy@163.com
  • 基金资助:
    国家科技部重点研发计划项目(2016YFC1000401);国家科技部重点研发计划项目(2016YFC1000408)

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

Yang-yang CHEN1,Yu-bo ZHOU2,3,Jing YANG4,Yu-meng HUA1,Peng-bo YUAN4,Ai-ping LIU1,*(),Yuan WEI4,*()   

  1. 1. Department of Social Medicine and Health Education, Peking University School of Public Health, Beijing 100191, China
    2. Institute of Reproductive and Child Health, Peking University, National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China
    3. Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China
    4. Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
  • Received:2022-01-27 Online:2022-06-18 Published:2022-06-14
  • Contact: Ai-ping LIU,Yuan WEI E-mail:apingliu@163.com;weiyuanbysy@163.com
  • Supported by:
    the National Key Research and Development Program of China(2016YFC1000401);the National Key Research and Development Program of China(2016YFC1000408)

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摘要：

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。

关键词: 双胎妊娠, C反应蛋白, 糖尿病，妊娠, 体质量指数

Abstract:

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.

Key words: Twin pregnancy, C-reactive protein, Diabetes, gestational, Body mass index

中图分类号: 

  • R714.256

表1

不同hsCRP水平双胎妊娠孕妇的基本特征"

Items Total (n=570) T1 (n=178) T2 (n=191) T3 (n=201) P
hsCRP/(mg/L), M (P25, P75) 1.94 (0.93, 4.21) 0.61 (0.64, 0.92) 1.86 (1.59, 2.33) 5.28 (3.99, 7.24)
Maternal age/years, M (P25, P75) 33 (31, 36) 32 (31, 36) 33 (31, 36) 34 (31, 36)
Nationality, n (%) 0.333
  Han 526 (92.3) 166 (93.3) 179 (93.7) 181 (90.0)
  Minority 44 (7.7) 12 (6.7) 12 (6.3) 20 (10.0)
Educational level, n (%) < 0.001
  High school and below 54 (9.5) 11 (6.2) 12 (6.3) 31 (15.4)ac, bc
  Bachelor 319 (56.0) 91 (51.1) 106 (55.5) 122 (60.7)
  Master and above 197 (34.6) 76 (42.7) 73 (38.2) 48 (23.9)
Couple income per year (10 000 yuan), n (%) 0.128
   < 12 141 (24.7) 36 (20.2) 42 (22.0) 63 (31.3)
  ≥12 103 (18.1) 35 (19.7) 32 (16.8) 36 (17.9)
  ≥20 139 (24.4) 46 (25.8) 45 (23.6) 48 (23.9)
  ≥30 187 (32.8) 61 (34.3) 72 (37.7) 54 (26.9)
Smoking (or passively), n (%) 0.483
  No 467 (81.9) 146 (82.0) 161 (84.3) 160 (79.6)
  Yes 103 (18.1) 32 (18.0) 30 (15.7) 41 (20.4)
Alcohol, n (%) 0.423
  No 516 (90.5) 158 (88.8) 177 (92.7) 181 (90.0)
  Yes 54 (9.5) 20 (11.2) 14 (7.3) 20 (10.0)
Pre-pregnant BMI, n (%) < 0.001
  Normal 421 (73.9) 154 (86.5) 150 (78.5) 117 (58.2)ac, bc
  Overweight or obesity 149 (26.1) 24 (13.5) 41 (21.5) 84 (41.8)
Parity, n (%) 0.954
  0 484 (84.9) 152 (85.4) 161 (84.3) 171 (85.1)
  1- 86 (15.1) 26 (14.6) 30 (15.7) 30 (14.9)
Aspirin use, n (%) 0.516
  No 441 (77.4) 134 (75.3) 153 (80.1) 154 (76.6)
  Yes 129 (22.6) 44 (24.7) 38 (19.9) 47 (23.4)
Conception mode, n (%) 0.052
  Nature 161 (28.3) 59 (33.3) 57 (29.8) 45 (22.4)
  Assisted reproductive technology 408 (71.7) 118 (66.7) 134 (70.2) 156 (77.6)
Chorionic, n (%) 0.870
  Dichorionic 398 (75.2) 121 (73.8) 140 (76.1) 137 (75.7)
  Monochorionic 131 (24.8) 43 (26.2) 44 (23.9) 44 (24.3)
Gestational weeks at blood drawing, M (P25, P75) 9 (8, 10) 8 (7, 10) 9 (8, 10) 9 (8, 10)ac
Gestational weight gain, n (%) 0.256
  In the range 228 (40.0) 73 (41.0) 80 (41.8) 75 (37.3)
  Above the range 282 (49.5) 91 (51.1) 94 (49.2) 97 (48.3)
  Below the range 60 (10.5) 14 (7.9) 17 (8.9) 29 (14.4)
GDM, n (%) 0.017
  No 390 (68.4) 136 (76.4) 127 (66.5) 127 (63.2)ac
  Yes 180 (31.6) 42 (23.6) 64 (33.5) 74 (36.8)

表2

血清hsCRP水平与GDM发生的关联"

Model Unadjusted Adjusted
T1 T2 T3 Ptrend T1 T2 T3 Ptrend
Model 1 Ref. 1.42 (1.02, 1.88)* 1.56 (1.15, 2.03)** 0.015 Ref. 1.42 (1.02, 1.89)** 1.54 (1.12, 2.02)** 0.022
Model 2 Ref. 1.38 (0.99, 1.84) 1.41 (1.02, 1.88)* 0.081 Ref. 1.38 (0.99, 1.85) 1.40 (1.00, 1.89) 0.089
Model 3 Ref. 1.44 (1.04, 1.91)* 1.58 (1.17, 2.06)** 0.012 Ref. 1.43 (1.03, 1.91)* 1.55 (1.13, 2.04)** 0.021

表3

不同BMI、孕期增重情况的hsCRP水平与GDM关系"

hsCRP tertiles BMI Gestational weight gain status
Normal Overweight or obesity In the range Above the range Below the range
n GDM, n (%) n GDM, n (%) n GDM, n (%) n GDM, n (%) n GDM, n (%)
Total 421 117 (27.79) 149 63 (42.28) 228 56 (24.56) 282 107 (37.94) 60 17 (28.33)
T1 154 35 (22.73) 24 7 (29.17) 73 13 (17.81) 91 27 (29.67) 14 2 (14.29)
T2 150 46 (30.67) 41 18 (43.90) 80 20 (25.00) 94 39 (41.49) 17 5 (29.41)
T3 117 36 (37.34) 84 38 (45.24) 75 23 (30.67) 97 41 (42.27) 29 10 (34.48)
PCMH=0.087 PCMH=0.014

表4

BMI、孕期增重情况对hsCRP水平和GDM关联的中介效应"

Items Mediation of BMI on the association Mediation of gestational weight gain on the association
T1 vs. T2 T2 vs. T3 T1 vs. T3 T1 vs. T2 T2 vs. T3 T1 vs. T3
Total effect 0.099*
(0.003, 0.190)		 0.028
(-0.074, 0.120)		 0.127***
(0.039, 0.210)		 0.100
(-0.011, 0.180)		 0.029
(-0.068, 0.100)		 0.129***
(0.037, 0.210)
Mediated effect 0.009*
(0.001, 0.020)		 0.024*
(0.010, 0.050)		 0.030***
(0.004, 0.050)		 0.001
(-0.007, 0.010)		 0.006
(-0.001, 0.020)		 0.006
(-0.001, 0.020)
Direct effect 0.091
(-0.004, 0.190)		 0.005
(-0.103, 0.100)		 0.097*
(0.017, 0.180)		 0.099
(-0.010, 0.180)		 0.023
(-0.076, 0.100)		 0.122***
(0.032, 0.200)
Proportion of mediation 8.59%
(-0.002, 1.460)		 83.80%
(-4.980, 7.810)		 23.84%***
(0.049, 0.660)		 0.76%
(-0.085, 0.160)		 20.54%
(-1.124, 1.850)		 4.77%
(-0.016, 0.190)

图1

BMI对hsCRP-GDM关联的中介效应分析"

表5

hsCRP与孕期增重对GDM的联合关联效应"

hsCRP & gestational weight gain n Unadjusted Adjusted
T1 & in the range 73 Reference Reference
T1 & above the range 91 1.67 (0.95, 2.68) 1.66 (0.93, 2.68)
T1 & below the range 14 0.80 (0.13, 2.34) 0.78 (0.13, 2.29)
T2 & in the range 80 1.40 (0.75, 2.40) 1.39 (0.73, 2.38)
T2 & above the range 94 2.33 (1.46, 3.38)*** 2.31 (1.44, 3.36)**
T2 & below the range 17 1.65 (0.59, 3.23) 1.66 (0.59, 3.24)
T3 & in the range 75 1.72 (0.96, 2.78) 1.68 (0.93, 2.74)
T3 & above the range 97 2.37 (1.50, 3.42)*** 2.31 (1.44, 3.37)**
T3 & below the range 29 1.94 (0.92, 3.27) 1.90 (0.89, 3.24)
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CN 11-4691/R
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