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749 The impact of obesity on the disease course of preeclampsia Emily Miller 1 , Alan Peaceman 1 1 Northwestern University, Maternal Fetal Medicine, Chicago, IL OBJECTIVE: Obesity is a well-established risk factor for the develop- ment of preeclampsia. Various possible causal etiologies have been proposed to explain this relationship. Insofar as these pathways to- ward preeclampsia may differ from the pathophysiology of pre- eclampsia 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-preg- nancy BMI 30.0 kg/m2). Clinical data pertaining to their pre- eclampsia 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 pro- teinuria). 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 94- 107) v 98 mm Hg (IQR 92-104), p0.001]. In addition, the non-obese group had a significantly increased risk of having an elevated AST (47% vs 32%, p0.001), an elevated ALT (25% vs 18%, p0.014), 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%, p0.006). CONCLUSION: Of the women that were identified with preeclampsia, the majority were obese. However women with obesity and pre- eclampsia 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 1 , Serkalem Tadesse 2 , Zhonghua Tang 3 , Seth Guller 3 1 Tufts University School of Medicine, Obstetrics & Gynecology, Boston, MA, 2 Tufts Medical Center, Obstetrics & Gynecology, Division of Maternal-Fetal Medicine, Boston, MA, 3 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 maternal- fetal 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 cytotro- phoblasts (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 pre- eclamptic 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 (n8). To mimic the increased iron level and hypoxic environment in PE, cells were supplemented with iron citrate (25M) and exposed to normoxic (NMX; 20% O 2 ) or hypoxic conditions (HPX; 2% O 2 for 24h. NGAL protein and mRNA levels were measured by western blot and RT- qPCR. 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 (p0.003) and 286.352.7 vs 80.613.9 (p0.001), respectively; (2) In CTs, iron supplementation increased NGAL expression under HPX (33.4-fold, p0.0019), but not NMX; (3) In CTs, iron supplementation increased NGAL mRNA levels 3-fold under NMX but 175-fold under HPX (60-fold higher com- pared with HPX alone). Thus, HPX increased NGAL mRNA and pro- tein expression in CTs in an iron-dependent manner. CONCLUSION: These data demonstrate that enhanced NGAL expres- sion 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. 751 Preeclampsia is a significant risk factor for long-term morbidity Guy Shalom 1 , Eyal Sheiner 2 , Ilana Shoham-Vardi 3 , Ruslan Sergienko 4 , Arnon Wiznitzer 5 , Michael Sherf 6 1 Soroka University Medical Center, Obstetrics and Gynecology, Beer-Sheva, Israel, 2 Soroka University Medical Center, Ben-Gurion University of the Negev, Department of Obstetrics and Gynecology, Beer-Sheva, Israel, 3 Epidemiology and Health Services Evaluation, Epidemiology and Health Services Evaluation, Beer-Sheva, Israel, 4 Ben Gurion University of the Begev, Epidemiology, Beer-Sheva, Israel, 5 Soroka University Medical Center, Department of Obstetrics and Gynecology, Beer-Sheva, Israel, 6 Soroka University Medical Center, Ob/Gyn, Beer-Sheva, Israel OBJECTIVE: The present study was aimed to evaluate long term mor- bidity of patients with preeclampsia. STUDY DESIGN: A retrospective cohort study was conducted, including women who gave birth between the years of 1988 to 1998, and had a follow-up until 2009. Data were extracted by linking a computerized database of hospitalizations with computerized database containing maternal records from the district hospital during the study period. The exposed group consisted of 2072 patients with preeclampsia (ei- ther mild or severe) in one or more of their pregnancies that were compared to 20742 patients without preeclampsia (non exposed group). Excluded from the study were patients with chronic hyper- tension and pre-gestational diabetes before the index pregnancy (in 1988 to 1998). Data were collected regarding subsequent hospitaliza- tions in internal medicine, oncology, nephrology, neurology, cardiac Poster Session V Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical-Disease www.AJOG.org S332 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012

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

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749 The impact of obesity on thedisease course of preeclampsiaEmily Miller1, Alan Peaceman1

1Northwestern University, Maternal Fetal Medicine, Chicago, ILOBJECTIVE: Obesity is a well-established risk factor for the develop-ment of preeclampsia. Various possible causal etiologies have beenproposed to explain this relationship. Insofar as these pathways to-ward preeclampsia may differ from the pathophysiology of pre-eclampsia in non-obese parturients, the clinical ramifications of thedisease may differ. This study was designed to assess whether there isa difference in the clinical presentation of preeclampsia between obeseand non-obese women.STUDY DESIGN: This is a retrospective cohort study of women whoreceived a diagnosis of pre-eclampsia. Women were categorized asobese (pre-pregnancy BMI � 30.0 kg/m2) or non-obese (pre-preg-nancy BMI � 30.0 kg/m2). Clinical data pertaining to their pre-eclampsia were abstracted from the chart, including gestational age atdelivery, neonatal birth weight, blood pressure ranges, and lab values(creatinine, liver function tests, uric acid, platelet count, level of pro-teinuria).RESULTS: Of the 874 women included, 531 (61%) were obese. Therewere no statistically significant differences in maternal age, gestationalage at delivery, BUN or creatinine levels, or amount of proteinuriabetween the two groups. While there was no difference in highestsystolic blood pressure recorded, the non-obese cohort had a highermedian maximum diastolic blood pressure [101 mm Hg (IQR 94-107) v 98 mm Hg (IQR 92-104), p�0.001]. In addition, the non-obesegroup 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 weretwice as likely to develop both a platelet count of less than 100,000 andLFTs more than double of normal, consistent with the diagnosis ofHELLP 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 pre-eclampsia had lab abnormalities less frequently and also lower peakdiastolic blood pressures. This suggests that the pathophysiology ofpreeclampsia may differ between obese and non-obese women.

750 Preeclampsia (PE) enhances NGAL expressionat fetal-maternal interface: role of iron and hypoxiaErrol Norwitz1, Serkalem Tadesse2, Zhonghua Tang3, Seth Guller3

1Tufts University School of Medicine, Obstetrics & Gynecology, Boston, MA,2Tufts Medical Center, Obstetrics & Gynecology, Division of Maternal-FetalMedicine, Boston, MA, 3Yale University School of Medicine, Obstetrics,Gynecology and Reproductive Sciences, New Haven, CTOBJECTIVE: PE is associated with both a substantial elevation in irondeposition and an aberrant maintenance of hypoxia at the maternal-fetal interface. Indeed, increases in serum iron and iron transportingproteins such as neutrophil gelatinase-associated lipocalin (NGAL)have been proposed as potential antecedents of clinical symptoms inPE. This study investigates for the first time the possible role of iron,hypoxia, and NGAL in the etiology of PE using cultures of cytotro-phoblasts (CTs) and decidual cells (DCs).STUDY DESIGN: To assess NGAL protein expression in PE, we analyzedplacental tissues from normotensive (GA: 31 [30-32] wks) vs pre-eclamptic patients (GA: 31 [28-32] wks) by immunohistochemistry(IHC) and H-score analysis. CTs and DCs were isolated and purifiedfrom normal term placentas delivered by cesarean (n�8). To mimicthe increased iron level and hypoxic environment in PE, cells weresupplemented with iron citrate (25M) and exposed to normoxic(NMX; 20% O2) or hypoxic conditions (HPX; 2% O2 for 24h. NGALprotein and mRNA levels were measured by western blot and RT-qPCR.RESULTS: (1) IHC revealed elevated NGAL protein expression in bothextravillous 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 increasedNGAL expression under HPX (33.4-fold, p�0.0019), but not NMX;(3) In CTs, iron supplementation increased NGAL mRNA levels3-fold under NMX but 175-fold under HPX (60-fold higher com-pared with HPX alone). Thus, HPX increased NGAL mRNA and pro-tein expression in CTs in an iron-dependent manner.CONCLUSION: These data demonstrate that enhanced NGAL expres-sion in EVT and decidua is a novel marker of PE. Further, our in vitrostudies suggest that CT NGAL levels are elevated in PE through aniron-dependent, HPX-driven mechanism that is mediated at the levelof gene transcription.

751 Preeclampsia is a significant riskfactor for long-term morbidityGuy Shalom1, Eyal Sheiner2, Ilana Shoham-Vardi3,Ruslan Sergienko4, Arnon Wiznitzer5, Michael Sherf6

1Soroka University Medical Center, Obstetrics and Gynecology, Beer-Sheva,Israel, 2Soroka University Medical Center, Ben-Gurion University of theNegev, Department of Obstetrics and Gynecology, Beer-Sheva, Israel,3Epidemiology and Health Services Evaluation, Epidemiology and HealthServices Evaluation, Beer-Sheva, Israel, 4Ben Gurion University of theBegev, Epidemiology, Beer-Sheva, Israel, 5Soroka University MedicalCenter, Department of Obstetrics and Gynecology, Beer-Sheva, Israel,6Soroka University Medical Center, Ob/Gyn, Beer-Sheva, IsraelOBJECTIVE: The present study was aimed to evaluate long term mor-bidity of patients with preeclampsia.STUDY DESIGN: A retrospective cohort study was conducted, includingwomen who gave birth between the years of 1988 to 1998, and had afollow-up until 2009. Data were extracted by linking a computerizeddatabase of hospitalizations with computerized database containingmaternal records from the district hospital during the study period.The exposed group consisted of 2072 patients with preeclampsia (ei-ther mild or severe) in one or more of their pregnancies that werecompared to 20742 patients without preeclampsia (non exposedgroup). Excluded from the study were patients with chronic hyper-tension and pre-gestational diabetes before the index pregnancy (in1988 to 1998). Data were collected regarding subsequent hospitaliza-tions in internal medicine, oncology, nephrology, neurology, cardiac

Poster Session V Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical-Disease www.AJOG.org

S332 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012