777 Maternal serum paraxanthine, a caffeine metabolite,and the risk of severe preeclampsiaKacey Eichelberger1, Arthur Baker2, Padmashree Woodham1,Sina Haeri3, Robert Strauss4, Alison Stuebe5

1University of North Carolina, Dept of ObGyn, Divison of Maternal-FetalMedicine, Obstetrics and Gynecology, Chapel Hill, NC, 2Memorial HealthUniversity Medical Center, Obstetrics and Gynecology, Savannah, GA,3University of North Carolina at Chapel Hill, Obstetrics and Gynecology,Chapel Hill, NC, 4University of North Carolina at Chapel Hill,Department of OBGYN, Obstetrics and Gynecology, Chapel Hill,NC, 5University of North Carolina, Obstetrics and Gynecology;Division of Maternal-Fetal Medicine, Chapel Hill, NCOBJECTIVE: The Generation R Study Group recently reported a re-duced risk of preeclampsia in pregnant women reporting 180-260mg/day of caffeine intake compared with women reporting �180 mg/day. No studies have measured the association between paraxanthine,the primary caffeine metabolite, and preeclampsia risk. Our objectivewas to assess the relationship between midgestation maternal serumparaxanthine and the risk of subsequent severe preeclampsia.STUDY DESIGN: We conducted a nested case-control study of 33women carrying singleton gestations with no chronic medical ill-nesses who subsequently developed severe preeclampsia, matched byage and race to 99 healthy controls. High-performance liquid chro-matography was used to measure maternal paraxanthine from bankedserum samples drawn at 16-20 weeks gestational age. We used multi-variate logistic regression to measure the association between serumparaxanthine and odds of severe preeclampsia.RESULTS: The median paraxanthine level in our cohort was 91 ng/mL(IQR 22-206). We identified serum paraxanthine levels above thelower limit of quantification (10 ng/mL) in 25/33 cases (76%) and88/99 controls (89%), Fishers Exact p�0.08. There was a trend to-wards lower paraxanthine levels in women who subsequently devel-oped severe preeclampsia as compared to controls (geometric mean52.46 vs. 83.10) but this did not reach statistical significance (p�0.11).Higher serum paraxanthine was associated with lower odds of severepreeclampsia (OR 0.72, 95% CI 0.48-1.08 per log paraxanthine stan-dard deviation).CONCLUSION: Consistent with previous reports, we found an inverseassociation between maternal caffeine intake, indexed by serumparaxanthine level, and severe preeclampsia, although our findingsdid not reach statistical significance. Larger studies are needed to con-firm this association.

778 Excessive placental Toll-like receptor 7/8 signalingcontributes to human and experimental preeclampsiaKaren Doersch1, Piyali Chatterjee1, Samantha Allen1,Shelley Kopriva1, Valorie Chiasson1, Brett Mitchell11Texas A&M Health Science Center, Internal Medicine, Temple, TXOBJECTIVE: Preeclampsia (PE) is a pregnancy-related disorder thatcomplicates about 10% of pregnancies and leads to health risks forboth mother and fetus. While the exact causes of PE remain elusive,recent studies suggest involvement of the immune system, specificallythe innate components residing at the maternal-fetal interface thatrespond to danger signals. It is unknown whether the single strandedRNA receptors TLR7 and TLR8 in the placenta are involved in thedevelopment of PE. We hypothesized that placentas from womenwith PE have increased TLR7, TLR8, and NFkB (a mediator of inflam-mation) activation and that stimulation of TLR7/8 would cause in-flammation in human cytotrophoblast (CTB) cells and PE in mice.STUDY DESIGN: TLR7, TLR8, and NFkB expression were measured inplacentas from PE and normotensive women by immunohistochem-istry (IHC). CTBs were treated with R837 (which stimulates TLR7)and CL097 (which stimulates both TLR7 and TLR8) for 6, 24, or 48hours and TLR7 and TLR8 activation was analyzed by Western blot.Placentas from mice treated with R837 or CL097, which exhibit PE-like symptoms, were analyzed by qPCR and Western blot.

RESULTS: Women with PE had a significant increase in placentalTLR7, TLR8, and NFkB expression compared to normotensivewomen. R837 treatment of CTBs increased TLR7 and NFkB, whileCL097 treatment markedly increased TLR7, TLR8, and NFkB. Micemade preeclamptic with R837 had a significant increase in placentalTLR7 gene expression (2.5-fold) and TLR7 and NFkB protein expres-sion. Preeclamptic CL097-treated mice had a significant increase inplacental TLR7 and TLR8 gene expression (�3-fold) and TLR7,TLR8, and NFkB protein expression.CONCLUSION: These results suggest that excessive placental TLR7/TLR8 activation plays a role in PE and inhibition of this signalingpathway may reduce the severity of PE.

779 Indication for delivery in pregnantwomen with chronic hypertensionKaren Wilson1, Scott Roberts1, DonaldMcIntire1, James M. Alexander1

1University of Texas Southwestern Medical Center,Obstetrics and Gynecology, Dallas, TXOBJECTIVE: To evaluate the indications for delivery in pregnantwomen with chronic hypertension when routine induction of labor atterm is not practiced for this subgroup of pregnant women.STUDY DESIGN: All women with chronic hypertension requiring med-ication for blood pressure control are referred to a specialty clinic. Atthe patients first visit, baseline evaluations are done of urine proteinand creatinine and a maternal echo is performed. Women are seenregularly at 3-4 week intervals until 20 weeks of gestation and thenthey are seen every 2 weeks until 36 weeks of gestation. After this timethe patient is seen on a weekly basis until delivery. Fetal growth eval-uations are done by ultrasound at 28-30 weeks and 34-36 weeks ofgestation. Routine induction of labor and antenatal surveillance is notdone. Specifically for this analysis, we compared maternal and neona-tal outcomes in pregnant women with chronic hypertension requiringmedications for blood pressure control to all other women who de-livered during January 2008 through December 2010.RESULTS: Outcomes were analyzed in 43,389 women. Women withchronic hypertension were more likely to have preterm deliveries andpreeclampsia but there was no difference between cohorts in the un-explained stillbirth and abruption rates. Infants born to women withchronic hypertension were more likely to be growth restricted butthere was no difference in neonatal outcomes when adjusted for ges-tational age.CONCLUSION: Women with chronic hypertension in pregnancy typi-cally develop an indication for delivery in the 36th week of gestation.This appears to be most commonly related to preeclampsia and fetalgrowth restriction. There was no difference in the stillbirth rate orneonatal outcomes when women were managed expectantly.

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 S343