The study, led by Natalie Holowko and colleagues from the Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, is the largest of its kind to date. It assessed how peri-conceptional glycaemic control influences the risk of preeclampsia among women with type 1 diabetes mellitus (T1DM), using national registry data from Sweden.
The population-based cohort included over 1.68 million singleton pregnancies between 2003 and 2019, of which 4,429 were in women with T1DM and more than 1.68 million in women without diabetes. Researchers linked the Swedish National Diabetes Register with other health registers to track outcomes, categorising glycaemic control according to HbA1c levels recorded within 90 days before or after conception. HbA1c was grouped as <48, 48–61, 62–75, and ≥76 mmol/mol.
The following were the key findings of the study:
- 16.8% of women with type 1 diabetes developed preeclampsia compared with 2.9% of women without diabetes (aRR 4.7).
- Risk of preeclampsia increased with higher peri-conceptional HbA1c levels: 11.6% (<48 mmol/mol), 23.3% (≥76 mmol/mol).
- Adjusted relative risk rose in a dose–response manner: HbA1c <48 mmol/mol (aRR 3.4), 48–61 mmol/mol (aRR 4.6), 62–75 mmol/mol (aRR 5.7), ≥76 mmol/mol (aRR 6.3).
- The term preeclampsia risk was 3.5 times higher in women with type 1 diabetes compared with women without diabetes.
- The risk of early preterm preeclampsia (<34 weeks) was 7.2 times higher in women with type 1 diabetes.
- Late preterm preeclampsia (34–36 weeks) was 9.9 times higher in women with type 1 diabetes.
- Women with type 1 diabetes remained at a higher risk of preeclampsia even with HbA1c levels within guideline-recommended targets.
- Optimal peri-conceptional glycaemic control was associated with the lowest risk of preeclampsia in women with type 1 diabetes.
The authors noted some limitations, including the fact that HbA1c values were typically recorded only once a year in the Swedish registry, potentially excluding some women with diabetes and introducing selection bias. Diagnosing preeclampsia in women with pre-existing kidney involvement, such as albuminuria, can also be complex due to overlapping symptoms. Sensitivity analyses, however, confirmed the robustness of the findings, even after excluding women with albuminuria or accounting for low-dose aspirin use, which can lower preterm preeclampsia risk. Another limitation was the absence of continuous glucose monitoring (CGM) data, which is now considered a more precise tool for managing diabetes in pregnancy.
Despite these caveats, the study provides strong evidence that type 1 diabetes is a major risk factor for preeclampsia, and that peri-conceptional glycaemic control plays a critical role in modifying that risk. The researchers stressed that while women with diabetes remain at elevated risk even when meeting guideline-recommended HbA1c targets, maintaining glucose levels as close to normal as possible around conception offers the best protection against preeclampsia, especially severe preterm forms.
Reference:
Holowko, N., Roos, N., Pasternak, B., Söderling, J., Neovius, M., Gudbjörnsdottir, S., Sandström, A., Ludvigsson, J. F., & Stephansson, O. Glycaemic Control in Women With Type 1 Diabetes and Preeclampsia Risk: A Nationwide Cohort Study. BJOG: An International Journal of Obstetrics & Gynaecology. https://doi.org/10.1111/1471-0528.18339
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