749: The impact of obesity on the disease course of preeclampsia

disease course of preeclampsia Emily Miller, Alan Peaceman Northwestern University, Maternal Fetal Medicine, Chicago, IL OBJECTIVE: Obesity is a well-established risk factor for the development of preeclampsia. Various possible causal etiologies have been proposed to explain this relationship. Insofar as these pathways toward preeclampsia may differ from the pathophysiology of preeclampsia in non-obese parturients, the clinical ramifications of the disease may differ. This study was designed to assess whether there is a difference in the clinical presentation of preeclampsia between obese and non-obese women. STUDY DESIGN: This is a retrospective cohort study of women who received a diagnosis of pre-eclampsia. Women were categorized as obese (pre-pregnancy BMI 30.0 kg/m2) or non-obese (pre-pregnancy BMI 30.0 kg/m2). Clinical data pertaining to their preeclampsia were abstracted from the chart, including gestational age at delivery, neonatal birth weight, blood pressure ranges, and lab values (creatinine, liver function tests, uric acid, platelet count, level of proteinuria). RESULTS: Of the 874 women included, 531 (61%) were obese. There were no statistically significant differences in maternal age, gestational age at delivery, BUN or creatinine levels, or amount of proteinuria between the two groups. While there was no difference in highest systolic blood pressure recorded, the non-obese cohort had a higher median maximum diastolic blood pressure [101 mm Hg (IQR 94107) v 98 mm Hg (IQR 92-104), p 0.001]. In addition, the non-obese group had a significantly increased risk of having an elevated AST (47% vs 32%, p 0.001), an elevated ALT (25% vs 18%, p 0.014), and thrombocytopenia (45% vs 30%). The non-obese women were twice as likely to develop both a platelet count of less than 100,000 and LFTs more than double of normal, consistent with the diagnosis of HELLP syndrome (6.7% v 2.8%, p 0.006). CONCLUSION: Of the women that were identified with preeclampsia, the majority were obese. However women with obesity and preeclampsia had lab abnormalities less frequently and also lower peak diastolic blood pressures. This suggests that the pathophysiology of preeclampsia may differ between obese and non-obese women. 750 Preeclampsia (PE) enhances NGAL expression at fetal-maternal interface: role of iron and hypoxia Errol Norwitz, Serkalem Tadesse, Zhonghua Tang, Seth Guller Tufts University School of Medicine, Obstetrics & Gynecology, Boston, MA, Tufts Medical Center, Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Boston, MA, Yale University School of Medicine, Obstetrics, Gynecology and Reproductive Sciences, New Haven, CT OBJECTIVE: PE is associated with both a substantial elevation in iron deposition and an aberrant maintenance of hypoxia at the maternalfetal interface. Indeed, increases in serum iron and iron transporting proteins such as neutrophil gelatinase-associated lipocalin (NGAL) have been proposed as potential antecedents of clinical symptoms in PE. This study investigates for the first time the possible role of iron, hypoxia, and NGAL in the etiology of PE using cultures of cytotrophoblasts (CTs) and decidual cells (DCs). STUDY DESIGN: To assess NGAL protein expression in PE, we analyzed placental tissues from normotensive (GA: 31 [30-32] wks) vs preeclamptic patients (GA: 31 [28-32] wks) by immunohistochemistry (IHC) and H-score analysis. CTs and DCs were isolated and purified from normal term placentas delivered by cesarean (n 8). To mimic the increased iron level and hypoxic environment in PE, cells were supplemented with iron citrate (25M) and exposed to normoxic (NMX; 20% O2) or hypoxic conditions (HPX; 2% O2 for 24h. NGAL protein and mRNA levels were measured by western blot and RTqPCR. RESULTS: (1) IHC revealed elevated NGAL protein expression in both extravillous trophoblast (EVT) and decidua in PE vs control (H-score: meanSEM): 375.175.7 vs 44.18.8 (p 0.003) and 286.352.7 vs 80.613.9 (p 0.001), respectively; (2) In CTs, iron supplementation increased NGAL expression under HPX (33.4-fold, p 0.0019), but not NMX; (3) In CTs, iron supplementation increased NGAL mRNA levels 3-fold under NMX but 175-fold under HPX (60-fold higher compared with HPX alone). Thus, HPX increased NGAL mRNA and protein expression in CTs in an iron-dependent manner. CONCLUSION: These data demonstrate that enhanced NGAL expression in EVT and decidua is a novel marker of PE. Further, our in vitro studies suggest that CT NGAL levels are elevated in PE through an iron-dependent, HPX-driven mechanism that is mediated at the level of gene transcription.