Eur J Obstet Gynecol Reprod Biol. 2026 Oct 14;327:115494. doi: 10.1016/j.ejogrb.2026.115494. Online ahead of print.

ABSTRACT

OBJECTIVE: To characterize serum sulfated glycosaminoglycan (GAG) abundance across preeclampsia (PE) severity and its association with uteroplacental hemodynamics and fetal outcomes.

STUDY DESIGN: Prospective cross-sectional study of 130 women at 30-36 weeks (50 with PE without severe features, 50 with PE with severe features, and 30 controls), enrolled from January 2022 to December 2023. PE was classified according to ACOG 2020 and ISSHP 2018. Total serum sulfated GAGs were quantified by DMMB colorimetry. Charge-based electrophoretic fractions were estimated by cellulose acetate electrophoresis. Because this method does not resolve chondroitin sulfate isomers or separate chondroitin from dermatan sulfate, we report only a heparan sulfate/heparin fraction and a combined galactosaminoglycan (chondroitin/dermatan sulfate) fraction. Uteroplacental Doppler and a six-component biophysical profile were assessed. Firth penalized logistic regression was the primary model.

RESULTS: Total sulfated GAGs declined with severity (controls 38.4 ± 6.2 vs. severe PE 14.3 ± 3.8 μg/mL; P < 0.001). In absolute concentration, both fractions declined (HS/heparin 8.4 ± 2.1 to 1.5 ± 0.7 μg/mL; galactosaminoglycan 30.2 ± 5.8 to 12.9 ± 3.7 μg/mL; both P < 0.001). The heparin sulfate fraction fell in both absolute and relative terms, whereas the galactosaminoglycan fraction rose only as a relative proportion. Doppler indices and placental dysfunction worsened across PE strata. In the primary Firth regression, a lower heparin sulfate fraction was associated with abnormal uteroplacental hemodynamics (aOR 2.68; 95% CI 1.21-5.94; P = 0.015). Smoking and antihypertensive therapy were not estimable.

CONCLUSION: Lower serum sulfated GAGs, particularly the heparan sulfate fraction, were associated with impaired placental hemodynamics in PE but tracked overall disease severity. These observational findings are limited by the method and are hypothesis-generating; they require replication with disaccharide-level profiling.

PMID:42887427 | DOI:10.1016/j.ejogrb.2026.115494