妊娠期糖尿病与子代新生儿期代谢物水平的关系

Association of maternal gestational diabetes mellitus with neonatal metabolites

目的:探讨孕母妊娠期糖尿病(gestational diabetes mellitus,GDM)对新生儿代谢物的影响。方法:采用回顾性队列研究设计,纳入2018年1月至12月在广东省佛山市妇幼保健院孕母诊断GDM并活产分娩的580例单胎新生儿(GDM组),按照孕妇年龄1∶1匹配的非GDM单胎孕妇的新生儿580例作为非GDM组。新生儿生后3~7 d内进行遗传代谢病筛查。比较组间代谢物的差异,分析GDM与新生儿代谢物水平间的关系。采用两独立样本t检验及多重线性回归模型进行统计学分析。结果:GDM组和非GDM组间新生儿代谢物中共有7种氨基酸及10种脂肪酸的差异有统计学意义,其中GDM组子代血清中6种氨基酸和8种脂肪酸水平升高,而胡椒酰胺[(140.79±32.60)与(150.26±35.46)μmol/L,t=-4.733,P<0.001]、棕榈酰肉碱[(2.59±0.81)与(2.73±0.82)μmol/L,t=-2.940,P=0.003]及二十四碳酰肉碱[(0.066±0.022)与(0.069±0.022)μmol/L,t=-1.937,P=0.042]水平下降。多重线性回归发现,校正母亲孕次、产次及新生儿出生体重和性别后,GDM与子代新生儿期3种氨基酸呈正相关,分别是半胱氨酸(β=0.012)、同型半胱氨酸(β=0.263)和亮氨酸(β=4.225);与2种氨基酸呈负相关,分别为甘氨酸(β=-6.271)和胡椒酰胺(β=-9.885)。GDM与子代新生儿期8种脂肪酸呈正相关,分别是丙酰肉碱(β=0.214)、丁酰肉碱(β=0.014)、3-羟基丁酰肉碱(β=0.006)、异戊酰肉碱(β=0.009)、3-羟基异戊酰肉碱(β=0.024)、二十六碳酰肉碱(β=0.001)、癸二烯酰肉碱(β=0.045)、十八碳二烯酰肉碱(β=0.128);与2种脂肪酸呈负相关,分别为棕榈酰肉碱(β=-0.119)和二十四碳酰肉碱(β=-0.002),差异均有统计学意义(P值均<0.05)。结论:GDM与多种新生儿氨基酸和脂肪酸代谢物水平存在相关关系,提示GDM可能影响子代生命早期的氨基酸和脂肪酸的代谢水平。

Objective To investigate the effects of gestational diabetes mellitus(GDM)on neonatal metabolites.Methods This retrospective cohort study recruited 580 singleton newborns who were born to women with GDM from January 2018 to December 2018 in Foshan Maternal and Child Health Care Hospital as the GDM group.Another 580 counterparts born to non-GDM singleton mothers with matching age were selected as the non-GDM group with an allocation ratio of 1 to 1.Neonatal genetic metabolic disease screening was performed within 3-7 days after birth.Two independent sample t-test,and multiple linear regression model were used for statistical analysis.Results There were significant differences in seven amino acids and 10 fatty acids levels between the GDM and non-GDM group.The serum levels of six amino acids and eight fatty acids were increased in the GDM group,while the levels of piperamide[(140.79±32.60)vs(150.26±35.46)μmol/L,t=-4.733,P<0.001],palmitoyl carnitine[(2.59±0.81)vs(2.73±0.82)μmol/L,t=-2.940,P=0.003],and carbamate[(0.066±0.022)vs(0.069±0.022)μmol/L,t=-1.937,P=0.042]were decreased compared with the non-GDM group.After adjusting for maternal gravidity,parity,neonatal birth weight,and gender,multivariate linear regression analysis showed that GDM was positively correlated with three amino acids levels,which were cysteine(ß=0.012),homocysteine(ß=0.263)and leucine(ß=4.225);and was negatively correlated with glycine(ß=-6.271)and piperamide level(ß=-9.885).With regard to the fatty acids,GDM was positively correlated with the neonatal propionyl carnitine(ß=0.214),butyryl carnitine(ß=0.014),3-hydroxybutyryl carnitine(ß=0.006),isovaleryl carnitine(ß=0.009),3-hydroxyisovaleryl carnitine(ß=0.024),hexadecanoyl carnitine(ß=0.001),decadienoyl carnitine(ß=0.045),octadecadienyl carnitine level(ß=0.128),but was negatively correlated with palmitoyl carnitine(ß=-0.119),and carbamate(ß=-0.002)(all P<0.05).Conclusions Correlations between maternal GDM and the levels of amino acids and fatty acids in neonates was noted in this study,suggesting that maternal GDM may affect the metabolism of amino acids and fatty acids in offspring at early stage of life.