Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Department of Pediatrics, Örebro University Hospital, Sweden.
BMJ. 2018 Jul 5;362:k2638. doi: 10.1136/bmj.k2638.
To examine the association between maternal type 1 diabetes and the risk of major birth defects according to levels of glycated haemoglobin (HbA1C) within three months before or after estimated conception.
Population based historical cohort study using nationwide health registers.
Sweden, 2003-15.
2458 singleton liveborn infants of mothers with type 1 diabetes and a glycated haemoglobin measurement within three months before or after estimated conception and 1 159 865 infants of mothers without diabetes.
Major cardiac and non-cardiac birth defects according to glycated haemoglobin levels.
122 cases of major cardiac defects were observed among 2458 infants of mothers with type 1 diabetes. Compared with 15 cases of major cardiac defects per 1000 infants of mothers without diabetes, the rates among infants of mothers with type 1 diabetes were 33 per 1000 for a glycated haemoglobin level of <6.5% (adjusted risk ratio 2.17, 95% confidence interval 1.37 to 3.42), 49 per 1000 for 6.5% to <7.8% (3.17, 2.45 to 4.11), 44 per 1000 for 7.8% to <9.1% (2.79, 1.90 to 4.12), and 101 per 1000 for ≥9.1% (6.23, 4.32 to 9.00). The corresponding adjusted risk differences were 17 (5 to 36), 32 (21 to 46), 26 (13 to 46), and 77 (49 to 118) cases of major cardiac defects per 1000 infants, respectively. 50 cases of major non-cardiac defects were observed among infants of mothers with type 1 diabetes. Compared with 18 cases of major non-cardiac defects per 1000 infants of mothers without diabetes, the rates among infants of mothers with type 1 diabetes were 22 per 1000 for a glycated haemoglobin level of <6.5% (adjusted risk ratio 1.18, 0.68 to 2.07), 19 per 1000 for 6.5% to <7.8% (1.01, 0.66 to 1.54), 17 per 1000 for 7.8% to <9.1% (0.89, 0.46 to 1.69), and 32 per 1000 for ≥9.1% (1.68, 0.85 to 3.33).
Among liveborn infants of mothers with type 1 diabetes, increasingly worse glycaemic control in the three months before or after estimated conception was associated with a progressively increased risk of major cardiac defects. Even with glycated haemoglobin within target levels recommended by guidelines (<6.5%), the risk of major cardiac defects was increased more than twofold. The risk of major non-cardiac defects was not statistically significantly increased at any of the four glycated haemoglobin levels examined; the study had limited statistical power for this outcome and was based on live births only.
根据妊娠估算前后三个月内糖化血红蛋白（HbA1C）水平，研究母亲 1 型糖尿病与主要出生缺陷风险之间的关系。
利用全国健康登记处进行基于人群的历史队列研究。
瑞典，2003-2015 年。
2458 名患有 1 型糖尿病的单胎活产婴儿，其母亲在妊娠估算前后三个月内有糖化血红蛋白测量值，以及 1159865 名无糖尿病母亲的婴儿。
根据糖化血红蛋白水平评估主要心脏和非心脏出生缺陷。
在患有 1 型糖尿病的 2458 名婴儿中，观察到 122 例主要心脏缺陷。与无糖尿病母亲的婴儿每 1000 例有 15 例主要心脏缺陷相比，糖化血红蛋白水平<6.5%的婴儿发生率为每 1000 例 33 例（调整风险比 2.17，95%置信区间 1.37 至 3.42），6.5%至<7.8%为 49 例（3.17，2.45 至 4.11），7.8%至<9.1%为 44 例（2.79，1.90 至 4.12），≥9.1%为 101 例（6.23，4.32 至 9.00）。相应的调整风险差异分别为每 1000 例婴儿 17（5 至 36）、32（21 至 46）、26（13 至 46）和 77（49 至 118）例主要心脏缺陷。在患有 1 型糖尿病的婴儿中，观察到 50 例主要非心脏缺陷。与无糖尿病母亲的婴儿每 1000 例有 18 例主要非心脏缺陷相比，糖化血红蛋白水平<6.5%的婴儿发生率为每 1000 例 22 例（调整风险比 1.18，0.68 至 2.07），6.5%至<7.8%为 19 例（1.01，0.66 至 1.54），7.8%至<9.1%为 17 例（0.89，0.46 至 1.69），≥9.1%为 32 例（1.68，0.85 至 3.33）。
在患有 1 型糖尿病的活产婴儿中，妊娠估算前后三个月内血糖控制情况越差，主要心脏缺陷的风险呈逐渐增加趋势。即使糖化血红蛋白处于指南推荐的目标水平（<6.5%），主要心脏缺陷的风险也增加了两倍以上。在研究的四个糖化血红蛋白水平中，主要非心脏缺陷的风险均无统计学显著增加；该研究对这一结果的统计能力有限，且仅基于活产婴儿。
