Maternal plasma syndecan-1: a biomarker for fetal growth restriction

Abstract

Objective

The identification of fetal growth disorders is an important clinical priority given that they increase the risk of perinatal morbidity and mortality as well as long-term diseases. A subset of small-for-gestational-age (SGA) infants are growth-restricted, and this condition is often attributed to placental insufficiency. Syndecan-1, a product of the degradation of the endothelial glycocalyx, has been proposed as a biomarker of endothelial damage in different pathologies. During pregnancy, a “specialized” form of the glycocalyx—the “syncytiotrophoblast glycocalyx”—covers the placental villi. The purpose of this study was to determine whether the concentration of maternal plasma syndecan-1 can be proposed as a biomarker for fetal growth restriction.

Study design

A cross-sectional study was designed to include women with normal pregnancy (n = 130) and pregnant women who delivered an SGA neonate (n = 50). Doppler velocimetry of the uterine and umbilical arteries was performed in women with an SGA fetus at the time of diagnosis. Venipuncture was performed within 48 h of Doppler velocimetry and plasma concentrations of syndecan-1 were determined by a specific and sensitive immunoassay.

Results

(1) Plasma syndecan-1 concentration followed a nonlinear increase with gestational age in uncomplicated pregnancies (R² = 0.27, p < .001); (2) women with a pregnancy complicated with an SGA fetus had a significantly lower mean plasma concentration of syndecan-1 than those with an appropriate-for-gestational-age fetus (p = .0001); (3) this difference can be attributed to fetal growth restriction, as the mean plasma syndecan-1 concentration was significantly lower only in the group of women with an SGA fetus who had abnormal umbilical and uterine artery Doppler velocimetry compared to controls (p = .00071; adjusted p = .0028). A trend toward lower syndecan-1 concentrations was also noted for SGA with abnormal uterine but normal umbilical artery Doppler velocimetry (p = .0505; adjusted p = .067); 4) among women with an SGA fetus, those with abnormal umbilical and uterine artery Doppler findings had a lower mean plasma syndecan-1 concentration than women with normal Doppler velocimetry (p = .02; adjusted p = .04); 5) an inverse relationship was found between the maternal plasma syndecan-1 concentration and the umbilical artery pulsatility index (r = −0.5; p = .003); and 6) a plasma syndecan-1 concentration ≤ 850 ng/mL had a positive likelihood ratio of 4.4 and a negative likelihood ratio of 0.24 for the identification of a mother with an SGA fetus who had abnormal umbilical artery Doppler velocimetry (area under the ROC curve 0.83; p < .001).

Conclusion

Low maternal plasma syndecan-1 may reflect placental diseases and this protein could be a biomarker for fetal growth restriction. However, as a sole biomarker for this condition, its accuracy is low.

Keywords:

• Diagnosis
• Doppler velocimetry
• endothelium
• glycocalyx
• inflammation
• intrauterine growth restriction
• placenta
• prediction
• pregnancy
• small for gestational age (SGA)
• syncytiotrophoblast
• ultrasound
• umbilical artery
• uterine artery

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported, in part, by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS); and, in part, with Federal funds from NICHD/NIH/DHHS under Contract [No. HHSN275201300006C].