737: First-trimester metabolomic signature markers and preeclampsia: effect of maternal smoking

and preeclampsia: effect of maternal smoking Anthony Odibo, Alison Cahill, Katherine Goetzinger, Linda Odibo, Methodius Tuuli, Dennis Dietzen Washington University in St. Louis, Department of Obstetrics and Gynecology, St. Louis, MO, Washington University in St Louis, Department of Pathology, St Louis, MO OBJECTIVE: Recent studies suggest that early assessment of metabolomic markers in maternal serum can predict pregnancies at risk for later development of preeclampsia. We sought to test the hypothesis that the profile of first-trimester metabolic biomarkers is differentially altered by maternal smoking status in women who later develop preeclampsia (PE) compared with non-preeclamptic controls. STUDY DESIGN: We conducted a nested-case control study within a prospective cohort of pregnant women followed from first-trimester to delivery. Cases that developed PE at any gestational age (GA) were compared to controls without PE, matched for GA within three days. Maternal blood obtained at 11-14 weeks gestation was analyzed for 40 acylcarnitine species (C2-C18 saturated, unsaturated, and hydroxylated) and 32 amino acids by LC tandem mass spectrometry. The metabolite levels for the cases and control were compared using Students t test, Mann-Whitney test, Chi-squared or Fischer exact test, stratified by maternal smoking status. RESULTS: We compared 41 cases with PE (including 8 smokers) with 41 controls (including 5 smokers). We found four metabolites [Hydroxyhexanoylcarnitine (C6OH), alanine, phenylalanine, and glutamate], that were significantly higher in the cases with PE compared with the control group. When stratified by smoking status, significant differences were noted in metabolic profiles with PE and the control groups across strata (6 metabolites reduced in smoking PE and 4 in smoking controls). For example, C6OH is elevated in PE compared with controls but reduced in both smoking controls and PE (see box plot). CONCLUSION: While metabolic signatures are promising tools in screening for PE in the first-trimester, our findings suggest that maternal smoking status should be adjusted for in future studies. 738 Angiotensinogen overexpression alters uteroplacental blood flow and leads to pregnancy induced hypertension and fetal growth restriction Antonio Frias, Jessica Hebert, Amy Schilling, Jonathan Lindner, Terry Morgan Oregon Health and Science University, Department of Obstetrics and Gynecology, Portland, OR, Oregon Health & Science University, Pathology, Portland, OR, Oregon Health & Science University, Cardiology, Portland, OR OBJECTIVE: Preeclampsia and intrauterine growth restriction often occur together and have similar placental pathology. A common human angiotensinogen (AGT) promoter variant [A( 6)] is linked with an increased risk of preeclampsia, IUGR and aberrant spiral artery remodeling. We hypothesized that increased maternal AGT causes abnormal uteroplacental blood flow with increased sflt-1 expression leading to pregnancy induced hypertension and IUGR. STUDY DESIGN: We used a transgenic mouse model constructed to mimic the A( 6) haplotype. Maternal mean arterial pressure was measured by radio-telemetry in transgenic and control mice before and during pregnancy. Placental and maternal serum plasma sflt-1 levels were measured by real-time PCR and ELISA. Umbilical artery S/D ratio was measured using VisualsonicVevo 660 at gestational day 15.5 (E15.5) and E18. Uteroplacental blood flow and flux rates were measured at day E15.5 in vivo using at least three pups per litter by microbubble-enhanced ultrasound. RESULTS: Transgenic mice develop pregnancy induced hypertension and have growth restricted progeny (p 0.05). Doppler ultrasound demonstrated absent end diastolic flow at E15.5 and E18 in transgenic dams but normal diastolic flow in controls. Placental blood flow flux rates were significantly different between genotypes (P 0.01). Controls had a distinct spiral artery and showed slow filling of the placental labyrinth with a five second delay compared with the uterine wall (Figure 1). In contrast, transgenic dams had no distinct spiral artery and showed nearly instantaneous filling of the labyrinth (Figure 1). Transgenic maternal serum and placentas overexpressed sflt-1 compared with controls (p 0.0001). CONCLUSION: Our murine model that overexpresses AGT at levels similar to the human haplotype results in pregnancy induced hypertension, fetal growth restriction, and elevated sflt-1 levels. Our novel real-time in vivo measurements reveal these findings may be a consequence of abnormal spiral artery remodeling and faster uteroplacental blood flow resulting in increased placental sflt-1 secretion into maternal blood. www.AJOG.org Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical-Disease Poster Session V