159 - Cytokines and Endothelin-1 serum levels during the first hour of life among neonates born to women with Preeclampsia and their association with Neonatal Thrombocytopenia and Bronchopulmonary Dysplasia

Publication Number: 159.4492

Christos-Georgios Kontovazainitis, 2nd Neonatal Department and Neonatal Intensive Care Unit (NICU), Aristotle University of Thessaloniki, "Papageorgiou" University Hospital, Thessaloniki, Greece, Athens, Attiki, Greece; Dimitra Gialamprinou, Aristotle University of Thessaloniki, Thessaloniki, Thessaloniki, Greece; Alexandra Fleva, Immunology and Histocompatibility Department, "Papageorgiou" University Hospital, Thessaloniki, Greece, Thessaloniki, Thessaloniki, Greece; Anastasia Giannakou, Immunology and Histocompatibility Department, "Papageorgiou" University Hospital, Thessaloniki, Greece, Thessaloniki, Thessaloniki, Greece; Maria Varsami, Immunology and Histocompatibility Department, "Papageorgiou" University Hospital, Thessaloniki, Greece, Thessaloniki, Thessaloniki, Greece; Maria-Elina Bessina, Immunology and Histocompatibility Department, "Papageorgiou" University Hospital, Thessaloniki, Greece, Thessaloniki, Thessaloniki, Greece; Abraham Pouliakis, 2nd Department of Pathology, National and Kapodistrian University of Athens, "Attikon" University Hospital, Athens, Greece, Athens, Attiki, Greece; Theodoros Theodoridis, 1st Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, "Papageorgiou" Hospital, Thessaloniki, Greece, Thessaloniki, Thessaloniki, Greece; Elisavet Diamanti, 2nd Neonatal Department and Neonatal Intensive Care Unit (NICU), Aristotle University of Thessaloniki, "Papageorgiou" University Hospital, Thessaloniki, Greece, Thessaloniki, Thessaloniki, Greece; Georgios Mitsiakos, 2nd Neonatal Department and Neonatal Intensive Care Unit (NICU), Aristotle University of Thessaloniki, "Papageorgiou" University Hospital, Thessaloniki, Greece, Thessaloniki, Thessaloniki, Greece

Background: Maternal Preeclampsia (PE) is associated with neonatal complications such as Thrombocytopenia at birth and Bronchopulmonary Dysplasia (BPD). Endothelial dysfunction, playing a key role in PE's pathogenesis, is characterized by placental Endothelin-1 (ET1) overexpression and is mediated by cytokines such as Interleukins-2,6,8 (IL2,6,8) and Tumor-Necrosis-Factor α (TNFα). The above do not cross the placenta. However, the chorionic villi cells are in contact with the fetal circulation, and in the case of PE's endothelial dysfunction, chorionic villi cells produce such cytokines, which can likewise insert the fetal circulation. Thus, fetuses of PE-mothers may experience storms of placenta-derived mediators, leading to analogous neonatal endothelial dysfunction.

Objective: We aimed to assess the association of maternal and neonatal IL2,6,8, TNFα, ET1 with neonatal thrombocytopenia at birth (PLT < 150 x109/L) and BPD.

Design/Methods: The observational study was conducted at Papageorgiou General Hospital in Thessaloniki for from March 2022 to March 2024. We compared cytokine and ET1 levels between 31 PE-women and 45 healthy pregnant controls and their neonates (34 and 47, respectively). Maternal samples were drawn during labor and always before placental delivery. Neonatal samples were drawn from a peripheral vein within the first hour of life after birth.

Results: No differences were found in maternal and neonatal baseline characteristics.
PE-women presented higher IL2,6 and ET1 levels, while their neonates presented higher IL2 and TNFα levels.
Among PE-neonates, neonatal thrombocytopenia at birth was associated with maternal IL2 (OR 1.75, p=0.04) and ET1 (OR 7.38, p=0.04). Maternal IL2 had an AUC value of 0.75 (sensitivity 67%, specificity 82%, cut-off point 4.81 pg/mL). Maternal ET1 had an AUC value of 0.75 (sensitivity 100%, specificity 54%, cut-off point 0.74 pg/mL).
Among PE-neonates, BPD was associated with neonatal IL2 at birth (OR 1.24, p=0.04) with an AUC value of 0.72 (sensitivity 86%, specificity 54%, cut-off point 4.81 pg/mL).

Conclusion(s): PE-neonates presented an altered inflammatory response during the 1st hour of life. Maternal ET1 and maternal IL2 presented significant sensitivity and specificity (respectively) regarding the prediction of thrombocytopenia at birth among PE-neonates. The latter may be attributed to PE-associated placental ischemia, resulting in fetal megakaryocytes' series suppression. Maternal PE may cause a neonatal IL2 increase within the 1st hour of life, leading probably to altered vascular remodeling and, thus, to a higher probability of BPD.

Table 1. Baseline characteristics of pregnant women and their neonates (Preeclampsia Group and Controls). Summary measures are expressed as "Mean ± SD – Standard Deviation" or "Median (IQR – Interquartile Range)" for numerical variables and as Numbers with their respective percentages (%) for categorical variables. P-values in bold indicate statistical significance at the level α=0.05.


Table 2. Maternal and Neonatal Cytokines and Endothelin-1 results. Summary measures are expressed as "Mean ± SD – Standard Deviation" or "Median (IQR – Interquartile Range)". P-values in bold indicate statistical significance at the level α=0.05.


Figure 1. ROC Curves.(A) ROC Curves showing the discrimination capability of Neonatal ET1 (within 1st hour of life) and Maternal IL2 and ET1 regarding the prediction for Neonatal Thrombocytopenia at birth (PLT < 150 x109). AUC values do not differ significantly. (B) ROC Curve showing the discrimination capability of Neonatal IL2 (within 1st hour of life) regarding the prediction for Bronchopulmonary Dysplasia’s development.
Abbreviations: ET1: Endothelin 1; IL2: Interleukin. 2; PLT: Platelet