Evaluating Serial Serum Levels of Endocan and Syndecan in Infants Born to Women with Hypertensive Disorders of Pregnancy

Background: This retrospective analysis of prospectively collected data investigates whether the presence and severity of hypertensive disorders of pregnancy (HDP) are associated with alterations in endocan and syndecan, endothelial biomarkers, in preterm infants during the first 6 weeks of life to explore how maternal HDP may influence neonatal endothelial remodeling. Endocan and syndecan are both markers of endothelial dysfunction; however, syndecan has not yet been studied in the neonatal population. Methods: Data was collected from preterm infants (< 33 weeks gestation) admitted to the neonatal intensive care unit (NICU) between November 2014 and February 2024. Endocan and syndecan levels were measured from blood samples obtained within the first 48 hours of life (Week 0) and then repeatedly at postnatal Weeks 1-6. Infants with a clinical history of chorioamnionitis were excluded given its potential confounding effect on systemic inflammation and endothelial function. Maternal data included maternal age, gravida, para, gestational age at delivery, ethnicity, BMI, route of delivery, and any hypertensive disorders of pregnancy, with their respective treatment if used. The specific hypertensive disorders included gestational hypertension, preeclampsia (with and without severe features), chronic hypertension, chronic hypertension with superimposed preeclampsia (with and without severe features), and HELLP syndrome. Infant data gathered included date of birth, sex, birthweight, head circumference, length, and Apgar scores at 1 and 5 minutes. Groups were compared at each time point by 2-tailed t-tests, corrected for multiple comparisons. Differences with p < 0.05 were considered significant. Results: Endocan and syndecan levels were analyzed across 7 postnatal time points in 269 preterm infants born to mothers with (n=115) and without (n=154) hypertensive disorders of pregnancy (HDP). In infants born to normotensive mothers, syndecan levels exhibited a marked and consistent decline over the first 6 postnatal weeks. Specifically, syndecan levels decreased from 194 ± 19 ng/mL at Week 0 to 73 ± 44 ng/mL at Week 6, suggesting a steady process of neonatal endothelial remodeling. In the HDP subgroups a similarly consistent decline was observed. For example, infants of mothers with preeclampsia with severe features showed a reduction of syndecan levels from 180 ± 86 ng/mL at Week 0 to 90 ± 32 ng/mL at Week 6. Comparable baseline and Week 6 values for the other hypertensive subtypes were also noted, underscoring that the consistent linear decrease in syndecan was evident across the entire HDP spectrum. In contrast, endocan levels were more variable. Infants born to normotensive mothers exhibited relatively stable endocan values over time (Week 0: 317 ± 260 pg/mL; Week 6: 325 ± 289 pg/mL), whereas infants born to mothers with severe preeclampsia showed a more pronounced decrease (Week 0: 266 ± 212 pg/mL; Week 4: 157 ± 151 pg/mL). Initial comparisons suggested lower endocan levels in the preeclampsia with severe features group at weeks 4 and 5 (p