Maternal Midpregnancy Glucose Levels and Risk of Congenital Heart Disease in Offspring.
Maternal Midpregnancy Glucose Levels and Risk of Congenital Heart Disease in Offspring.
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DOI：
10.1001/jamapediatrics.2015.2831
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发表时间：
2015-12
期刊：
影响因子：
26.1
通讯作者：
Shaw GM
中科院分区：
文献类型：
--
作者：
Priest JR;Yang W;Reaven G;Knowles JW;Shaw GM
母亲糖尿病与后代患先天性心脏病（CHD）的风险之间存在良好的相关性。虽然2型糖尿病或妊娠期糖尿病的临床诊断是CHD的强危险因素，但葡萄糖和胰岛素代谢的亚临床异常在一般人群中很常见，也可能导致CHD的风险。我们探讨了后代中两种不同的CHD表型与妊娠中期血糖和胰岛素测量的潜在关联。这是一项病例对照研究，来自加州南部和中部的277名孕妇，她们的婴儿患有法洛四联症（ToF）（n=55）、d-大动脉转位（dTGA）（n=42）或无CHD的正常婴儿（n=180），测量与随机非空腹中期妊娠血液样本中的母体葡萄糖代谢相关的血液分析物。我们假设，与母亲糖尿病相关的血液分析物的连续测量与心脏畸形的几率有关。我们通过经验证的放射免疫法测定血清胰岛素和葡萄糖水平。多变量逻辑回归模型估计这些水平和病例状态之间的关联。相对于无心脏畸形婴儿的母体血糖水平，我们观察到，在包括胰岛素的模型中，母体血糖水平与ToF的比值密切相关（校正比值比7.54，95%CI 2.30-24.69），但与dTGA无关（校正OR 1.16，95%CI 0.28-4.79）。这些结果代表了葡萄糖作为连续变量与特定心脏畸形几率的直接相关性。血清葡萄糖和ToF几率之间的相关性表明，需要对妊娠早期胰岛素信号和葡萄糖代谢所带来的风险进行额外的流行病学和机制研究。
There is a well-described association between maternal diabetes and risk of congenital heart disease (CHD) in offspring. Though the clinical diagnoses of Type 2 diabetes or gestational diabetes are strong risk factors for CHD, sub-clinical abnormalities of glucose and insulin metabolism are common within the general population and could also confer risk for CHD. We explored the potential association of two different CHD phenotypes in offspring with midpregnancy measures of glucose and insulin. This is a case-control study from a cohort of 277 pregnant women in southern and central California carrying infants with tetralogy of Fallot (ToF) (n=55), d-transposition of the great arteries (dTGA) (n=42), or normal infants without CHD (n=180), Measurement of blood analytes related to maternal glucose metabolism taken from random non-fasting second trimester blood samples. We hypothesize that continuous measures of blood analytes related to maternal diabetes are related to odds of cardiac malformations. We measured serum insulin by a validated radioimmunoassay and glucose levels. Multivariable logistic regression models estimated the association between these levels and case status. Relative to maternal blood glucose levels of infants without cardiac malformations, we observed that maternal blood glucose levels in models including insulin were strongly associated with odds of ToF (adjusted Odds Ratio 7.54, 95%CI 2.30–24.69), but not with dTGA (adjusted OR 1.16, 95%CI 0.28–4.79). These results represent a direct correlation of glucose as a continuous variable to odds of specific cardiac malformations. The association between serum glucose and odds of ToF indicates the need for additional epidemiological and mechanistic investigations into the risk conferred by insulin signaling and glucose metabolism during early pregnancy.