OBJECTIVE To investigate the association between maternal glycemic control and the risk of congenital malformations in offspring of women with type 1 diabetes and to examine whether there is a hemoglobin A 1C (Hb A 1C ) threshold value at which the risk for malformations increases significantly. METHODS Analyses were performed on data from a multinational, observational cohort of 1,908 liveborn offspring of women with type 1 diabetes recruited in early pregnancy from 17 countries between 2013 and 2018. Offspring with malformations were identified according to European Surveillance of Congenital Anomalies version 1.4 and categorized as having one or more major malformations or minor malformations exclusively. The association between first-trimester Hb A 1C levels and the risk of congenital malformations was investigated with splines in crude and adjusted logistic regression models. RESULTS In total, 11.9% of the offspring (n=227) of women with type 1 diabetes had congenital malformations, including 2.1% (n=40) with at least one severe malformation. Women giving birth to offspring with malformations had a higher prevalence of psychiatric disorders (13.2% vs 7.2%, P <.01), thyroid disorders (33.0% vs 26.7%, P <.05), and folic acid supplementation (87.1% vs 77.7%, P <.01). The Hb A 1C levels in the first trimester were similar (median 6.8% [interquartile range 6.3-7.6%] vs 6.7% [6.2-7.6%], P =.13) compared with women giving birth to offspring without malformations. The spline analysis illustrated a curvilinear association between Hb A 1C levels and the risk of malformations with no clear threshold values. Higher first-trimester Hb A 1C levels were associated with an increased risk of malformations (crude odds ratio [OR] 1.13, 95% CI, 1.01-1.27, adjusted odds ratio [aOR] 1.29, 95% CI, 1.10-1.51) and major malformations (crude OR 1.49, 95% CI, 1.23-1.81, aOR 1.57, 95% CI, 1.15-2.09). CONCLUSION An increased risk for congenital malformations was curvilinearly associated with higher Hb A 1C levels in early pregnancy among women with type 1 diabetes without any threshold values identified. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov , NCT01892319.

中文翻译：

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1 型糖尿病女性的血糖控制和先天性畸形风险。


目的 探讨母体血糖控制与 1 型糖尿病女性后代先天性畸形风险的相关性，并检查是否存在血红蛋白 A 1C （Hb A 1C） 阈值，达到该阈值时畸形风险显著增加。方法 对 1,908 年至 17 年间从 17 个国家招募的 17 名妊娠早期女性活产后代的跨国观察队列数据进行了分析。根据欧洲先天性异常监测 1.4 版确定畸形后代，并将其归类为具有一种或多种严重畸形或仅具有轻微畸形。在粗略和调整的 logistic 回归模型中用样条研究妊娠早期 Hb A 1C 水平与先天性畸形风险之间的关联。结果 总共 11.9% 的 1 型糖尿病女性后代 （n=227） 患有先天性畸形，其中 2.1% （n=40） 至少有一种严重畸形。生育畸形后代的妇女精神疾病患病率较高 （13.2% vs 7.2%，P <.01）、甲状腺疾病 （33.0% vs 26.7%，P <.05） 和叶酸补充剂 （87.1% vs 77.7%，P <.01）。与生育无畸形后代的妇女相比，妊娠早期的 Hb A 1C 水平相似 （中位数 6.8% [四分位距 6.3-7.6%] vs 6.7% [6.2-7.6%]，P =.13）。样条分析表明 Hb A 1C 水平与畸形风险之间存在曲线关联，但没有明确的阈值。妊娠早期 Hb A 1C 水平较高与畸形风险增加相关 （粗比值比 [OR] 1.13,95% CI，1.01-1。27，校正比值比 [aOR] 1.29,95% CI，1.10-1.51）和主要畸形（粗 OR 1.49,95% CI，1.23-1.81，aOR 1.57,95% CI，1.15-2.09）。结论 在 1 型糖尿病妇女中，先天性畸形风险增加与妊娠早期 Hb A 1C 水平升高无关，未确定任何阈值。临床试验注册 ClinicalTrials.gov ， NCT01892319.