The Influence of Gestational Diabetes on Neurodevelopment of Children in the First Two Years of Life: A Prospective Study

ObjectiveAnalyze the relation of gestational diabetes and maternal blood glucose levels to early cognitive functions in the first two years of life.MethodsIn a prospective Singaporean birth cohort study, pregnant women were screened for gestational diabetes at 26–28 weeks gestation using a 75-g oral glucose tolerance test. Four hundred and seventy three children (n = 74 and n = 399 born to mothers with and without gestational diabetes respectively) underwent neurocognitive assessments at 6, 18, and/or 24 month, including electrophysiology during an attentional task and behavioral measures of attention, memory and cognition.ResultsGestational diabetes is related to left hemisphere EPmax amplitude differences (oddball versus standard) at both six (P = 0.039) and eighteen months (P = 0.039), with mean amplitudes suggesting offspring of mothers with gestational diabetes exhibit greater neuronal activity to standard stimuli and less to oddball stimuli. Associations between 2-hour maternal glucose levels and the difference in EPmax amplitude were marginal at 6 months [adjusted β = -0.19 (95% CI: -0.42 to +0.04) μV, P = 0.100] and significant at 18 months [adjusted β = -0.27 (95% CI: -0.49 to -0.06) μV, P = 0.014], and the EPmax amplitude difference (oddball-standard) associated with the Bayley Scales of Infant and toddler Development-III cognitive score at 24 months [β = 0.598 (95% CI: 0.158 to 1.038), P = 0.008].ConclusionGestational diabetes and maternal blood glucose levels are associated with offspring neuronal activity during an attentional task at both six and eighteen months. Such electrophysiological differences are likely functionally important, having been previously linked to attention problems later in life.

**研究目标**：探讨妊娠糖尿病（gestational diabetes）与孕产妇血糖水平和婴幼儿出生后前两年早期认知功能的关联。
**研究方法**：本研究依托一项新加坡前瞻性出生队列研究，于妊娠26~28周时采用75克口服葡萄糖耐量试验（75-g oral glucose tolerance test）对孕妇进行妊娠糖尿病筛查。本研究共纳入473名儿童，其中74名母亲患有妊娠糖尿病，399名母亲无妊娠糖尿病；这些儿童分别在6、18及/或24月龄时接受神经认知评估，评估内容包括注意力任务中的电生理检测，以及注意力、记忆与认知的行为学测量。
**研究结果**：妊娠糖尿病与婴幼儿6月龄（P=0.039）及18月龄（P=0.039）时左半球EPmax振幅差（偏差刺激vs标准刺激）存在关联；平均振幅结果显示，妊娠糖尿病母亲所生子女对标准刺激的神经元活动更强，而对偏差刺激的神经元活动更弱。孕产妇2小时血糖水平与EPmax振幅差的关联在6月龄时处于临界水平[校正后β=-0.19，95%置信区间（CI）：-0.42~0.04 μV，P=0.100]，在18月龄时具有统计学显著性[校正后β=-0.27，95%置信区间（CI）：-0.49~-0.06 μV，P=0.014]；24月龄时，EPmax振幅差（偏差刺激-标准刺激）与贝利婴幼儿发育量表第三版（Bayley Scales of Infant and Toddler Development-III）认知得分存在关联[β=0.598，95%置信区间（CI）：0.158~1.038，P=0.008]。
**研究结论**：妊娠糖尿病与孕产妇血糖水平均与婴幼儿6、18月龄时注意力任务中的神经元活动存在关联。此类电生理差异可能具有重要功能意义，既往研究已证实其与日后的注意力障碍存在关联。