Predictive ability of serum advanced glycation end products at 11 to 13 weeks of gestation for early-onset preeclampsia

Minako Goto; Sho-Ichi Yamagishi; Takanori Matsui; Keiko Koide; Hiroko Takita; Mayumi Tokunaka; Akihiko Sekizawa

doi:10.1016/j.xagr.2022.100052

Predictive ability of serum advanced glycation end products at 11 to 13 weeks of gestation for early-onset preeclampsia

AJOG Glob Rep. 2022 Feb 26;2(2):100052. doi: 10.1016/j.xagr.2022.100052. eCollection 2022 May.

Authors

Minako Goto¹, Sho-Ichi Yamagishi², Takanori Matsui³, Keiko Koide¹, Hiroko Takita¹, Mayumi Tokunaka¹, Akihiko Sekizawa¹

Affiliations

¹ Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan (Drs Goto, Koide, Takita, Tokunaka, and Sekizawa).
² Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan (Dr Yamagishi).
³ Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan (Dr Matsui).

Abstract

Background: Placental hypoxia and resultant oxidative stress have been associated with the development of preeclampsia. Oxidative stress promotes the formation of advanced glycation end products.

Objective: This study aimed to assess whether serum levels of advanced glycation end products during the early stage of pregnancy are a predictive biomarker of early-onset and late-onset preeclampsia.

Study design: This was a nested case-control study that included 6 women with early-onset preeclampsia, 21 women with late-onset preeclampsia, and 50 age- and body mass index-matched healthy female control subjects. All women enrolled in the study had a complete medical history, including mean arterial pressure and uterine artery pulsatility index measurements. Furthermore, the women underwent blood chemistry analysis, including circulating levels of advanced glycation end products, soluble fms-like tyrosine kinase-1, and placental growth factor. Clinical measurements and biochemistry were evaluated at 11 to 13 and 19 to 24 weeks of gestation.

Results: The median serum concentrations of advanced glycation end products at 11 to 13 weeks of gestation were significantly higher in patients with early-onset preeclampsia than in those with late-onset preeclampsia and control subjects (6.62 vs 4.10 vs 3.77; P<.05), but no significant difference was found in advanced glycation end products at 19 to 24 weeks of gestation among the 3 groups. The advanced glycation end product-to-placental growth factor ratio in the first trimester of pregnancy was significantly higher in patients with early-onset preeclampsia than in those with late-onset preeclampsia or control subjects (0.78 vs 0.10 vs 0.10; P<.05). The area under the receiver operating characteristic curve values for patients with early-onset preeclampsia were 0.782 (95% confidence interval, 0.522-0.922), 0.855 (95% confidence interval, 0.433-0.978), and 0.925 (95% confidence interval, 0.724-0.983) for the advanced glycation end product and placental growth factor levels and advanced glycation end product-to-placental growth factor ratios, respectively. This population achieved a 100% detection rate for predicting early-onset preeclampsia at a screen-positive rate of 10% by combining the advanced glycation end product-to-placental growth factor ratio and the mean arterial pressure.

Conclusion: The study results suggested that an elevated advanced glycation end product-to-placental growth factor ratio and mean arterial pressure at 11 to 13 weeks of gestation could be a potential biomarker for predicting the future development of early-onset preeclampsia.

Keywords: advanced glycation end product; biomarker; early-onset preeclampsia; first-trimester screening; mean arterial pressure; placental growth factor; uterine artery pulsatility index.