1
RAGE, -secretases [ADAM 10&17] and -secretases [PS 1&2] were quantified by real-time RT-PCR. CB levels of sRAGE and esRAGE were determined by ELISA. Western blot with N-(extracellular) and C-(intracellular) terminus specific antibodies was used to detect sRAGE variants generated by - and -secretases, respectively. RESULTS: 1) There was a significant difference in birthweight (P.001) but not GA among groups; 2) In all groups, the level of placental FL-RAGE mRNA was more abundant than that of esRAGE (P.001); 3) The expression levels of FL-RAGE and esRAGE were not affected by either sPE or IUGR; 4) ADAM-10 and PS-1&2 mRNA levels were significantly decreased in IUGR fetuses independent of sPE (P.05 for all), implying low proteolytic activity; 5) CB total sRAGE, but not esRAGE, was significantly decreased in IUGR (P.006); 6) Multiple N- and C-terminus RAGE variants were seen in CB, with significant changes in banding pattern in IUGR and sPE, suggesting alternative cleavage sites in these conditions. CONCLUSION: A defective enzymatic processing of the RAGE receptor may explain the low levels of sRAGE in the CB of fetuses with IUGR. 403 A hypoxia gene signature in maternal blood detects fetal hypoxia in-utero in severe preterm growth restriction Clare Whitehead 1 , Susan Walker 1 , Sonali Mendis 1 , Stephen Tong 1 1 Mercy Hospital for Women, University Of Melbourne Department of Obstetrics and Gynaecology, Melbourne, Australia OBJECTIVE: Fetal hypoxia is the hallmark of severe fetal growth restric- tion (FGR). Ultrasound surveillance improves outcomes in FGR, but accurate detection of fetal hypoxia in-utero remains challenging. A clinical biomarker that can accurately determine the presence and degree of fetal hypoxia, may reduce perinatal morbidity and mortal- ity. RNA of feto-placental origin is detectable in maternal blood and reflects placental gene expression. We measured hypoxia-induced RNA in the maternal blood, to develop a blood test to detect the hypoxic fetus whilst still in-utero. STUDY DESIGN: We prospectively collected serial samples of maternal blood from pregnancies complicated by severe preterm FGR and ges- tation-matched appropriately grown controls. Severe FGR was de- fined as estimated fetal weight 10th centile at 34 weeks gestation, and abnormal ultrasound velocimetry of umbilical arteries / fetal vasculature. Blood samples were collected at each ultrasound assess- ment. Whole genome microarray were performed to develop a hyp- oxia gene signature in the maternal blood, and this signature was validated using RT-PCR. RESULTS: Gene ontology analysis revealed an increased expression of hypoxia-induced genes in the maternal blood from FGR cases com- pared to controls. RT-PCR confirmed that upregulation of the hyp- oxia gene signature (HIF1, HIF2, Adrenomedullin and LDH-A) successfully differentiated FGR cases from healthy controls. Further- more, the hypoxia gene signature reflected deteriorating fetal well- being as evidenced by worsening fetal umbilical artery velocimetry. Finally, there was a significant correlation between the hypoxia gene signature and the fetal pH at delivery. Figure 1 demonstrates the im- proved prediction of fetal pH by the hypoxia gene signature, than ultrasound assessment prior to delivery. CONCLUSION: The hypoxia gene signature in maternal blood shows increased expression in FGR, detects deteriorating fetal well-being and correlates closely with fetal pH at delivery. Thus, we have devel- oped a maternal blood test that may be used to optimally time delivery in severe preterm FGR. 404 Timing of delivery of the anomalous fetus– effects on neonatal outcomes Dzhamala Gilmandyar 1 , Brittany Paivanas 1 , Amy Hoeft MacDonald 1 , Tina Jensen 2 , Oluwateniola Brown 2 , J. Christopher Glantz 1 , Eva K. Pressman 1 , Loralei L. Thornburg 1 1 University of Rochester, Obstetrics and Gynecology, Rochester, NY, 2 University of Rochester School of Medicine and Dentistry, Obstetrics & Gynecology, Rochester, NY OBJECTIVE: The theorized advantage of daytime delivery to increase personnel/resource availability and shorten time to surgical repair for anomalous fetuses leads to high rates of scheduled daytime deliveries. We evaluated whether neonatal outcomes for non-lethal anomalous fetuses differed by timing of delivery. STUDY DESIGN: Retrospective evaluation of non-lethal anomalous fe- tuses, delivered 23 weeks gestation and 500 grams at single insti- tution with level III NICU between 1/2000 and 12/2010. Time of de- livery was stratified into Day (7am to 7pm Monday-Friday) and N/W (7 pm to 7am, or weekend). Anomalies were stratified by primary affected organ system: cardiac (N 118), CNS (N20), facial (N21) GI (N42), GU (N13), and musculoskeletal (N6). For all groups, infant 5-min Apgar score, NICU admission, perinatal mortality, im- mediate ventilation, ventilation 6 hours, antibiotic administration, length of stay (LOS) and time from birth to initial operative repair (TTR) were assessed. Chi-square, Mann-Whitney U, and t-testing were used for univariate analysis with p0.05 for significance. RESULTS: Of the 220 anomalous fetuses, 101 were Day, 119 N/W. There was no difference in low 5-min Apgar score, NICU admit, peri- natal mortality, immediate ventilation, ventilation 6 hours, or an- tibiotic administration for any group. TTR was significantly lower for Day in all patients, but not for GI or cardiac groups. LOS was signif- icantly lower for Day in GI group but not for all or cardiac. Post hoc power indicates an 80% power to detect a difference in LOS 12 days. CONCLUSION: There were no statistically significant differences in neo- natal outcomes for most anomalies based on time of delivery. How- ever, Day delivery did decrease time to surgery for all patients and LOS for GI anomalies. Daytime delivery may shorten the interval to initial operative repair for patients with fetal anomalies and LOS for GI anomalies. Poster Session III Doppler Assessment, Fetus, Prematurity www.AJOG.org S188 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012

403: A hypoxia gene signature in maternal blood detects fetal hypoxia in-utero in severe preterm growth restriction

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RAGE, �-secretases [ADAM 10&17] and �-secretases [PS 1&2] werequantified by real-time RT-PCR. CB levels of sRAGE and esRAGEwere determined by ELISA. Western blot with N-(extracellular) andC-(intracellular) terminus specific antibodies was used to detectsRAGE variants generated by �- and �-secretases, respectively.RESULTS: 1) There was a significant difference in birthweight(P�.001) but not GA among groups; 2) In all groups, the level ofplacental FL-RAGE mRNA was more abundant than that of esRAGE(P�.001); 3) The expression levels of FL-RAGE and esRAGE were notaffected by either sPE or IUGR; 4) ADAM-10 and PS-1&2 mRNAlevels were significantly decreased in IUGR fetuses independent of sPE(P�.05 for all), implying low proteolytic activity; 5) CB total sRAGE,but not esRAGE, was significantly decreased in IUGR (P�.006); 6)Multiple N- and C-terminus RAGE variants were seen in CB, withsignificant changes in banding pattern in IUGR and sPE, suggestingalternative cleavage sites in these conditions.CONCLUSION: A defective enzymatic processing of the RAGE receptormay explain the low levels of sRAGE in the CB of fetuses with IUGR.

403 A hypoxia gene signature in maternal blood detectsfetal hypoxia in-utero in severe preterm growth restrictionClare Whitehead1, Susan Walker1, Sonali Mendis1, Stephen Tong1

1Mercy Hospital for Women, University Of Melbourne Departmentof Obstetrics and Gynaecology, Melbourne, AustraliaOBJECTIVE: Fetal hypoxia is the hallmark of severe fetal growth restric-tion (FGR). Ultrasound surveillance improves outcomes in FGR, butaccurate detection of fetal hypoxia in-utero remains challenging. Aclinical biomarker that can accurately determine the presence anddegree of fetal hypoxia, may reduce perinatal morbidity and mortal-ity. RNA of feto-placental origin is detectable in maternal blood andreflects placental gene expression. We measured hypoxia-inducedRNA in the maternal blood, to develop a blood test to detect thehypoxic fetus whilst still in-utero.STUDY DESIGN: We prospectively collected serial samples of maternalblood from pregnancies complicated by severe preterm FGR and ges-tation-matched appropriately grown controls. Severe FGR was de-fined as estimated fetal weight �10th centile at � 34 weeks gestation,and abnormal ultrasound velocimetry of umbilical arteries �/� fetalvasculature. Blood samples were collected at each ultrasound assess-ment. Whole genome microarray were performed to develop a hyp-oxia gene signature in the maternal blood, and this signature wasvalidated using RT-PCR.RESULTS: Gene ontology analysis revealed an increased expression ofhypoxia-induced genes in the maternal blood from FGR cases com-pared to controls. RT-PCR confirmed that upregulation of the hyp-oxia gene signature (HIF1�, HIF2�, Adrenomedullin and LDH-A)successfully differentiated FGR cases from healthy controls. Further-more, the hypoxia gene signature reflected deteriorating fetal well-being as evidenced by worsening fetal umbilical artery velocimetry.Finally, there was a significant correlation between the hypoxia genesignature and the fetal pH at delivery. Figure 1 demonstrates the im-proved prediction of fetal pH by the hypoxia gene signature, thanultrasound assessment prior to delivery.CONCLUSION: The hypoxia gene signature in maternal blood showsincreased expression in FGR, detects deteriorating fetal well-beingand correlates closely with fetal pH at delivery. Thus, we have devel-oped a maternal blood test that may be used to optimally time deliveryin severe preterm FGR.

404 Timing of delivery of the anomalousfetus–effects on neonatal outcomesDzhamala Gilmandyar1, Brittany Paivanas1, Amy HoeftMacDonald1, Tina Jensen2, Oluwateniola Brown2, J. ChristopherGlantz1, Eva K. Pressman1, Loralei L. Thornburg1

1University of Rochester, Obstetrics and Gynecology, Rochester,NY, 2University of Rochester School of Medicine and Dentistry,Obstetrics & Gynecology, Rochester, NYOBJECTIVE: The theorized advantage of daytime delivery to increasepersonnel/resource availability and shorten time to surgical repair foranomalous fetuses leads to high rates of scheduled daytime deliveries.We evaluated whether neonatal outcomes for non-lethal anomalousfetuses differed by timing of delivery.STUDY DESIGN: Retrospective evaluation of non-lethal anomalous fe-tuses, delivered �23 weeks gestation and �500 grams at single insti-tution with level III NICU between 1/2000 and 12/2010. Time of de-livery was stratified into Day (7am to 7pm Monday-Friday) and N/W(7 pm to 7am, or weekend). Anomalies were stratified by primaryaffected organ system: cardiac (N� 118), CNS (N�20), facial (N�21)GI (N�42), GU (N�13), and musculoskeletal (N�6). For all groups,infant 5-min Apgar score, NICU admission, perinatal mortality, im-mediate ventilation, ventilation �6 hours, antibiotic administration,length of stay (LOS) and time from birth to initial operative repair(TTR) were assessed. Chi-square, Mann-Whitney U, and t-testingwere used for univariate analysis with p�0.05 for significance.RESULTS: Of the 220 anomalous fetuses, 101 were Day, 119 N/W.There was no difference in low 5-min Apgar score, NICU admit, peri-natal mortality, immediate ventilation, ventilation �6 hours, or an-tibiotic administration for any group. TTR was significantly lower forDay in all patients, but not for GI or cardiac groups. LOS was signif-icantly lower for Day in GI group but not for all or cardiac. Post hocpower indicates an 80% power to detect a difference in LOS �12 days.CONCLUSION: There were no statistically significant differences in neo-natal outcomes for most anomalies based on time of delivery. How-ever, Day delivery did decrease time to surgery for all patients and LOSfor GI anomalies. Daytime delivery may shorten the interval to initialoperative repair for patients with fetal anomalies and LOS for GIanomalies.

Poster Session III Doppler Assessment, Fetus, Prematurity www.AJOG.org

S188 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2012