812: maternal mortality from cardiac disease in pregnancy: outcomes from an obstetrical critical...
TRANSCRIPT
RESULTS: Nephrin and podocalyxin were barely measurable in theurine specimens from normal pregnant women and from chronichypertension. In PE, urinary nephrin and podocalyxin concentrationswere significantly higher than those in normal pregnancy and chronichypertension (p�0.01), and their levels were highly correlated to eachother, y � 4.611x � 327,491, r2 � 0.595. Nephrin and podocalyxinwith urine protein concentrations were also highly correlated, y �257.354x � 297.898, r2 � 0.746 for nephrin and y � 31.115x �10.640, r2 � 0.390 for podocalyxin, respectively. �ig-h3 was detectedin the urine specimens from PE but undetectable in normal pregnancyand pregnancy complicated with chronic hypertension. In PE, urinary�ig-h3 levels were also highly correlated to nephrin and podocalyxinconcentrations, y � 117.069x � 260.337, r2 � 0.515 for nephrin andy � 18.571x � 41.694, r2 � 0.463 for podocalyxin.CONCLUSION: These results provide strong evidence that specific podo-cyte protein shedding is associated with glomerular barrier dysfunc-tion in PE. Urinary �ig-h3 excretion indicates that increased TGF- �activity might be involved in the pathology of renal dysfunction in PE.Nephrin, podocalyxin, and �ig-h3 could serve as surrogate biomark-ers of glomerular barrier dysfunction in PE.
810 Aberrant O-linked glycosylation in preeclampsiaShannon K. Flood Nichols1, Peter G.Napolitano1, Danielle L. Ippolito2
1Madigan Healthcare System, Department of Obstetrics andGynecology, Tacoma, WA, 2Madigan Healthcare System,Department of Clinical Investigation, Tacoma, WAOBJECTIVE: Normal pregnancy is associated with a systemic inflam-matory response, but this effect is exaggerated in preeclampsia. De-fects in inflammatory protein glycosylation are characteristic of manydisease states associated with a maladaptive immune response. Wehypothesized that patients with preeclampsia would have aberrantplasma protein glycosylation patterns detectable early in pregnancy.STUDY DESIGN: Plasma was prospectively collected throughout gesta-tion from 300 women. Six normotensive and eleven preeclampsiacases were selected after review of antepartum records. Plasma pro-teins were pretreated with glycosidase enzymes or buffer control andseparated by gel electrophoresis. Plasma glycoprotein content wasquantified by glycan immunolabeling. Protein identity was assessedby Western blot.RESULTS: Glycoprotein profiles from preeclampsia plasma proteinswere significantly different from normotensive controls in all threetrimesters. A protein migrating at approximately 35 kDa was moreheavily glycosylated in women with preeclampsia than normotensivecontrols. Glycan staining was sensitive to enzymatic deglycosylationwith O-glycosidases but not N-glycosidases. A protein migrating at amolecular weight coincident with C1 inhibitor was sensitive to O-gly-cosidase treatment but not quantifiably different in preeclampsia rel-ative to normotensive controls.CONCLUSION: O-linked glycosylation patterns differed significantly inpreeclampsia patient plasma relative to normotensive controls. Theseresults suggest the utility of O-linked glycosylation in early diagnosisand therapeutic intervention in preeclampsia.
811 The impact of body mass index on serum magnesiumsulfate levels in women receiving seizure prophylaxisCarmen Tudela1, Donald McIntire1, James M. Alexander1
1University of Texas Southwestern Medical Center,Obstetrics and Gynecology, Dallas, TXOBJECTIVE: To determine the impact of body mass index (BMI) onserum magnesium levels in women receiving infusions for eclampsiaprophylaxis.STUDY DESIGN: This is a retrospective study from 2009 to 2011 lookingat serum levels in relation to BMI in all women receiving magnesiumsulfate infusions for seizure prophylaxis. Women receiving magne-sium receive a 6 gram intravenous load followed by a 2 gram per hourcontinuous infusion. Serum magnesium levels are defined as sub-
therapeutic at less than 4.9mg/dl, therapeutic from 4.9 to 8.4mg/dland supratherapeutic at 8.5mg/dl or greater. Women who have a sub-therapeutic serum magnesium level at 4 hours have their infusion rateincreased to 3 grams per hour. Women who have a supratherapeuticlevel or who show signs or symptoms of toxicity have their infusionsdecreased or discontinued until resolution of symptoms or until asubtherapeutic level occurs. All women have a 12 hour serum magne-sium level drawn after the initial IV bolus, and in subtherapeuticwomen, after the dose change.RESULTS: During the study period, 2,141 women received magnesiumsulfate for seizure prophylaxis and had serum magnesium levelsdrawn. One thousand five hundred and six women were identified asobese and 266 (18%) were subtherapeutic 4 hours after initiation andhad their infusions increased. At 12 hours, 1,424 (95%) were thentherapeutic. Further serum magnesium levels according to BMI areillustrated in the table.CONCLUSION: The majority of women (84%) therapeutic at 4 hoursremained so at 12 hours. A significant subset of women (91%) whowere supratherapeutic at 12 hours had been therapeutic at 4 hours,independent of BMI.
812 Maternal mortality from cardiac disease in pregnancy:outcomes from an obstetrical critical care unit in PanamaCarlos Montufar1, Alfredo Gei2
1Complejo Hospitalario Dr. Arnulfo Arias Madrid. Caja Panamea delSeguro Social, Unidad de Cuidados Especiales de Ginecologa yObstetricia, Panama, Panama, 2The Methodist Hospital ofHouston, Division of Maternal-Fetal Medicine, Houston, TXOBJECTIVE: The objective of this study was to describe the outcomes ofpregnant women with functionally significant cardiac disease at anObstetrical Critical Care Unit in Latin America (Panama).STUDY DESIGN: Prospective cohort of pregnant women with decom-pensated cardiac disease treated at an Obstetrical Critical Care Unit inPanama City. The analysis was restricted to women with NYHAclasses II and higher.RESULTS: Between January 1996 and June 2011, 88 women with de-compensated cardiac disease during pregnancy/puerperium were ad-mitted to a specialized Obstetrical Critical Care Unit for management.The mean maternal age at admission was 31 (�/� 4.6) years. Allpatients received prenatal care. The mean number of prenatal visitswas 7.4 visits. Twenty-eight patients were NYHA class II; 45 patientswere class III and 15 patients were class IV. Thirty-five cases (39.7%)were related to rheumatic valvular disease. The mean gestational ageat delivery was 36 (�/� 3.4) weeks. The maternal mortality was 4.5%(4/88). The deaths were related to pulmonary thromboembolism in 2patients despite anticoagulation with heparin (a case of mechanic mi-tral valve and a case of peripartum cardiomyopathy); right ventricularfailure in one case of severe pulmonary hypertension; and one case ofaortic dissection with cardiac tamponade on a previously healthy pa-tient. All deaths occurred during postpartum period; 3 / 4 during PPD
Poster Session V Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical-Disease www.AJOG.org
S356 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012
1. Two autopsies were performed confirming mechanical valvethrombosis and pulmonary embolism.CONCLUSION: Pregnant woman with cardiac disease have a higher riskof death during the postpartum period. In this series rheumatic val-vular disease was related to 50% of the maternal deaths.
813 Pregnancy outcomes in women with elevated freetriiodothyronine (fT3) during the first half of pregnancyCarmen Tudela1, Brian Casey1, DonaldMcIntire1, F. Gary Cunningham2
1University of Texas Southwestern Medical Center, Obstetrics andGynecology, Dallas, TX, 2The University of Texas SouthwesternMedical Center, Obstetrics and Gynecology, Dallas, TXOBJECTIVE: To assess pregnancy outcomes in women identified withelevated fT3 levels during the first half of pregnancy and comparethem to euthyroid women with normal range fT3 levels.STUDY DESIGN: Between November 2000 and April 2003, all womenwho presented for prenatal care underwent thyroid screening. Excessserum was frozen and stored at -80 degrees Celsius. Samples from17,298 women without clinical hypothyroidism and who had beenscreened in the first 20 weeks of gestation and delivered a singletoninfant weighing 500g or more were analyzed using a chemilumines-cent assay for multiple thyroid analytes including fT3. Pregnancy out-comes in women with fT3 values above the 97.5th percentile for ges-tational age were compared to women with fT3 values greater than the2.5th and less than the 97.5th percentiles. Pregnancy outcomes inthese women were further stratified according to thyrotropin (TSH)level and risk.RESULTS: The upper thresholds for fT3 ranged from 5.08 to 6.05pg/mL during the first half of pregnancy. When compared to womenwith normal fT3 (n�16,430) those with elevated fT3 (n�434) were atincreased risk for fetal death (1% vs. 0.5%, P � 0.012) See figure belowfor odds of fetal death according to fT3 and stratified by TSH level.CONCLUSION: Isolated elevated fT3 values during pregnancy are asso-ciated with an increase in perinatal mortality. This difference persistsin women with a normal TSH and high fT3.
814 Evidence that endoglin and transforminggrowth factor-beta (TGF�) participate in epithelial-to-mesenchymal transition (EMT) of extravilloustrophoblasts in placenta accretaChristina M. Duzyj1, Irina A. Buhimschi1, Christine Laky1,Genevieve Cozzini1, Guomao Zhao1, Mark Wehrum1, ChristianM. Pettker1, Sonya S. Abdel-Razeq1, Catalin S. Buhimschi1
1Yale University, Ob/Gyn & Reprod Sci., New Haven, CTOBJECTIVE: Activation of the EMT process is central to acquisition ofan invasive phenotype by epithelial cancer cells. Overexpression ofEndoglin (Eng), a ligand of the TGF� receptor system, and of TGF�proteins has been linked to EMT. Placental trophoblasts express Engand TGF� proteins, and thus in placenta accreta may be involved in
signaling pathways responsible for the invasive behavior of the ex-travillous trophoblasts (EVTs).STUDY DESIGN: A cross-sectional study was conducted to evaluate thematernal serum level of soluble Eng (sEng) in 17 women (GA: 29[23-34] wks) with histologically-confirmed trophoblast hyperinva-sion of the myometrium (accreta, n�3; increta, n�11; percreta,n�3). Samples from women with normal placentation (n�14) andplacenta previa (n�30) served as controls. sEng was assessed by ELISAand data was corrected for GA. Myometrial-villous sections, placentaltissues, and bed biopsies of women with normal and abnormal pla-centation were immunostained for vimentin (mesenchymal marker),cytokeratin-7 (epithelial marker), Eng, TGF�1 and TGF�2 proteins.Histological scoring analysis was employed.RESULTS: 1) Compared to controls, women with advanced placentalinvasion (increta & percreta) had lower serum levels of sEng(P�.005); 2) EVTs of accreta cases displayed positive staining for bothvimentin and cytokeratin consistent with EMT; 3) Increased intervil-lous space sEng immunostaining was observed only in women withabnormal invasion (accreta vs. normal vs. previa P�.019); 4) AccretaEVTs showed higher number of intra-cytoplasmic Eng-positive gran-ules compared to normal placental bed biopsies (P�.02); 5) Myome-trial TGF�1 staining was near-absent in the areas heavily populated byEVTs (P�.001) with no significant differences observed for TGF�2.CONCLUSION: In placenta accreta the Eng-TGF� system likely plays arole in promoting the invasive phenotype of EVTs. Decreased mater-nal systemic levels and increased intervillous staining for sEng pointtoward a complex mechanism of entrapment and processing of Eng atthe site of excessive trophoblast invasion.
815 Subsequent pregnancy outcomes in women previouslydiagnosed with subclinical hypothyroidismDavid Nelson1, Brian M. Casey1, F. Gary Cunningham1
1The University of Texas Southwestern MedicalCenter, Obstetrics and Gynecology, Dallas, TXOBJECTIVE: To evaluate pregnancy outcomes in women with previ-ously identified subclinical hypothyroidism during a previous preg-nancy.STUDY DESIGN: Between November 2000 and April 2003, all womenwho presented for prenatal care underwent thyroid screening at ourintuition. Excess serum was frozen and stored at 80 degrees Celsius.Samples from 17,298 women without clinical hypothyroidism whohad been screened in the first 20 weeks of gestation and who delivereda singleton infant weighing � 500-grams were evaluated using achemiluminescent assay for multiple thyroid analyses. Women withTSH values at or above 3.0 mu/L and a normal range free T4 (0.86 1.9ng/dL) were identified to have subclinical hypothyroidism duringtheir index pregnancy. Pregnancy data was then obtained on all pa-tients returning for a subsequent delivery. Return pregnancy out-comes in women previously identified with subclinical hypothyroid-ism is compared to those identified to be euthyroid.RESULTS: Of the 17,298 women previously screened, 6,985 (40%) re-turned and delivered a singleton infant at our hospital. This groupincludes 230 (38.4%) of the previously identified 598 subclinical hy-pothyroid women and 6,645 (41.5%) of the 16,011 euthyroid womenidentified by thyroid screening. See table below for pertinent positivefindings.CONCLUSION: Women previously identified with subclinical hypothy-roidism are at increased risk of diabetes complicating a subsequentpregnancy. There appears to be an increased risk for fetal death afterthe diagnosis of subclinical hypothyroidism.
www.AJOG.org Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical-Disease Poster Session V
Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology S357