1型糖尿病患者全孕程持续葡萄糖监测参数及产前血糖水平与新生儿低血糖发生的相关性

Association of continuous glucose monitoring indicators during pregnancy and antepartum glucose with the risk of neonatal hypoglycemia in women with type 1 diabetes mellitus

目的:探讨1型糖尿病(T1DM)患者全孕程持续葡萄糖监测(CGM)参数及产前血糖水平与新生儿低血糖发生的相关性。方法:本研究为多中心、前瞻性、观察性队列研究,自2015年1月至2017年12月在全国11家医院招募T1DM合并妊娠患者作为研究对象,采用CGM监测孕期血糖,记录产前2 h毛细血管血糖和新生儿结局。本研究纳入完成全孕程CGM的T1DM患者73例,根据分娩后新生儿血糖值(新生儿低血糖定义为新生儿血糖<2.2 mmol/L),分为新生儿低血糖组(14例)和新生儿血糖正常组(59例)。比较两组间全孕程糖化血红蛋白(HbA 1c)、CGM血糖参数[平均血糖、葡萄糖在目标范围内时间(TIR)、葡萄糖高于目标范围时间(TAR 1>7.8 mmol/L、TAR 2>13.9 mmol/L)、葡萄糖低于目标范围时间(TBR)、血糖标准差(SDBG)、平均血糖波动幅度(MAGE)、变异系数(CV)]、产前2 h血糖水平、分娩时孕周以及新生儿结局[出生体重、出生身长、早产率、新生儿重症监护病房(NICU)入住率]的差异。组间比较采用独立样本 t检验、秩和检验、 χ^(2)检验和Fisher精确检验法。采用多因素logistic回归模型分析新生儿低血糖发生的影响因素。 结果:相较新生儿血糖正常组,新生儿低血糖组孕母孕早期日间平均血糖[分别为(6.91±0.71)和(6.38±0.81)mmol/L, t=2.041, P<0.05]、孕早期TAR 2[分别为0.81%(0,4.36%)和0(0,0.64%), Z=2.064, P<0.05]、孕早期MAGE[分别为(6.42±3.24)和(4.60±1.67)mmol/L, t=2.137, P<0.05]、产前2 h血糖水平[分别为(7.75±2.22)和(6.13±2.10)mmol/L, t=2.324, P<0.05]升高,差异均具有统计学意义。新生儿低血糖组的早产率[分别为35.71%(5/14)和11.86%(7/59), χ^(2)=4.686, P<0.05]和NICU入住率[分别为71.43%(10/14)和32.20%(19/59), χ^(2)=5.725, P<0.05]高于新生儿血糖正常组,差异均具有统计学意义。多因素logistic回归分析提示,孕母产前2 h血糖是新生儿低血糖的独立影响因素(OR=2.23,95%CI 1.09~4.54, P<0.05)。 结论:T1DM患者孕早期平均血糖、TAR和MAGE与新生儿低血糖的发生相关,产前2 h血糖水平与新生儿低血糖的发生独立相关。

ObjectiveTo investigate the association between continuous glucose monitoring(CGM)during pregnancy and antepartum glucose with the risk of neonatal hypoglycemia in women with type 1 diabetes mellitus(T1DM).MethodsThis study was a multicenter,prospective,observational cohort study.Pregnant women with T1DM from 11 hospitals nationwide were enrolled from January 2015 to December 2017.CGM was used for glycemic control in pregnancy.Antepartum 2-hour capillary blood glucose and neonatal outcomes were recorded.A total of 73 women who used CGM during pregnancy were included in the study and divided into the neonatal hypoglycemia group(14 cases)and the neonatal normoglycemia group(59 cases)based on neonatal capillary glucose(neonatal hypoglycemia defined as<2.2 mmol/L)after delivery.Data on maternal glycated hemoglobin A 1c(HbA 1c),CGM metrics[mean blood glucose,time in range(TIR),time above range(TAR 1>7.8 mmol/L,TAR 2>13.9 mmol/L),time below range(TBR),standard deviation of blood glucose(SDBG),mean amplitude of glucose excursions(MAGE),coefficient of variation(CV)]during pregnancy,antepartum 2-hour blood glucose levels,gestational age at delivery,and neonatal obstetric outcomes[birth weight,birth length,premature delivery,neonatal intensive care unit(NICU)admission]were compared between groups.Comparisons between groups were made using the two independent samples t test,rank sum test,χ^(2) test and Fisher exact test.The influencing factors of neonatal hypoglycemia were analyzed by multivariate logistic regression models.ResultsCompared with neonatal normoglycemia group,women in the neonatal hypoglycemia group had higher mean blood glucose[(6.91±0.71)vs.(6.38±0.81)mmol/L,t=2.041,P<0.05],TAR 2[0.81%(0,4.36%)vs.0(0,0.64%),Z=2.064,P<0.05],and MAGE[(6.42±3.24)vs.(4.60±1.67)mmol/L,t=2.137,P<0.05]in the first trimester(P<0.05).Antepartum 2-hour blood glucose was higher in the neonatal hypoglycemia group[(7.75±2.22)vs.(6.13±2.10)mmol/L,t=2.324,P<0.05].The incidences of preterm birth[35.71%(5/14)vs.11.86%(7/59),χ^(2)=4.686,P<0.05]and NICU admission[71.43%(10/14)vs.32.20%(19/59),χ^(2)=5.725,P<0.05]were higher in the neonatal hypoglycemia group than in the neonatal normoglycemia group(P<0.05).The multivariate logistic regression analysis revealed that antepartum 2-hour blood glucose was the independent influencing factor of neonatal hypoglycemia(OR=2.23,95%CI 1.09-4.54,P<0.05).ConclusionsIncreased mean blood glucose,TAR,and MAGE in the first trimester were associated with a higher risk of neonatal hypoglycemia in pregnant women with T1DM.Antepartum 2-hour blood glucose was independently associated with the risk of neonatal hypoglycemia.