血糖控制与 1 型糖尿病女性先天畸形风险。

Glycemic Control and Risk of Congenital Malformations in Women With Type 1 Diabetes.

机构信息

Departments of Endocrinology and Obstetrics, Center for Pregnant Women With Diabetes, Rigshospitalet, and the Department of Clinical Medicine and the Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Novo Nordisk A/S, Søborg, and the Copenhagen Phase IV Unit, Department of Clinical Pharmacology, and the Center for Clinical Research and Prevention, Copenhagen University Hospital, Frederiksberg, Denmark.

出版信息

Obstet Gynecol. 2024 Nov 1;144(5):725-732. doi: 10.1097/AOG.0000000000005722. Epub 2024 Sep 5.

DOI:10.1097/AOG.0000000000005722

PMID:39236320

Abstract

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.

摘要

目的

研究 1 型糖尿病女性的血糖控制与后代先天畸形风险之间的关系，并探讨是否存在血红蛋白 A1C（HbA1C）阈值，超过该阈值会显著增加畸形风险。

方法

对 2013 年至 2018 年间来自 17 个国家的 1908 名 1 型糖尿病女性在孕早期招募的多国家、观察性队列的活产后代数据进行分析。根据欧洲先天畸形监测系统 1.4 版确定畸形儿，并将其分为有或无一种或多种重大畸形。使用简单线性和调整后的逻辑回归模型中的样条分析，调查孕早期 HbA1C 水平与先天畸形风险之间的关联。

结果

11.9%（227 名）的 1 型糖尿病女性所生后代患有先天性畸形，其中 2.1%（40 名）有至少一种严重畸形。有畸形儿的女性患精神障碍的比例（13.2% vs. 7.2%，P<.01）、甲状腺疾病（33.0% vs. 26.7%，P<.05）和叶酸补充（87.1% vs. 77.7%，P<.01）的比例较高。与无畸形后代的女性相比，孕早期 HbA1C 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）。样条分析显示，HbA1C 水平与畸形风险之间存在曲线关系，没有明确的阈值。孕早期较高的 HbA1C 水平与畸形风险增加相关（未经调整的优势比[OR] 1.13，95%置信区间[CI]，1.01-1.27，调整后的 OR[aOR]1.29，95%CI，1.10-1.51）和主要畸形（未经调整的 OR 1.49，95%CI，1.23-1.81，调整后的 OR[aOR]1.57，95%CI，1.15-2.09）。