CONCLUSION: Of the first trimester screen positive patients who ac-cessed prenatal diagnosis through the California Prenatal ScreeningProgram, 18.75% were found to have a pregnancy with a chromosomeabnormality. Patients with a screen positive result for trisomy 18 hada much higher risk of abnormality, particularly if the Down syndromescreening result was also positive.

595 NIPDT registry–a critical utilization of non-invasiveprenatal diagnosis test recently introduced toclinical practiceOssie Geifman-Holtzman1, Janet Berman2, Amen L Ness3, AmyCohen4, Richard Fischer5, Amanda Carre1, Stuart Weiner6

1Drexel College of Medicine, Obstetrics & Gynecology, Philadelphia, PA,2Temple School of Medicine, Obstetrics & Gynecology, Philadelphia, PA,3Saint Peters University Hospital, Obstetrics & Gynecology, New Brunswick,NJ, 4Einstein Medical Center, Genetics & Obstetrics/ Gynecology,Philadelphia, PA, 5Cooper University Hospital, Obstetrics & Gynecology,Camden, NJ, 6Thomas Jefferson University Hospital, Obstetrics &Gynecology, Philadelphia, PAOBJECTIVE: To evaluate the accuracy and utilization of noninvasiveprenatal diagnosis test (NIPDT) using fetal DNA in maternal bloodand to establish a multicenter registry to accomplish this aim.STUDY DESIGN: NIPDT by using fetal DNA in maternal blood to diag-nose chromosomal aneuploidy is currently available and its utiliza-tion is rapidly expanding. We collected data from 6 centers and tab-ulated it by patient age, gestational age (GA), indication, maternalserum screen, ultrasound finding. IRB approval was obtained. Wehave also established the NIPDT Registry to accomplish the abovegoal.RESULTS: A total of 175 patients underwent testing over the past 3months. Tests were performed at 11-13 weeks (12%), at 14-17 weeks(36%), at 18-22 (40%) weeks, and at 23-25 (12%) weeks’ gestation.The following indications were used to perform the test: Maternal age(above 35) 54% , Abnormal maternal serum screening 41%, Abnor-mal ultrasound finding 27% Positive family or personal history 4%. Atmaternal age of less than 35 about 77%, 15% and 8% were testedbecause of abnormal ultrasound finding, abnormal serum screen orboth abnormal and others, respectively. Inconclusive results were re-ported to be between 3.5%-5% possible causes: testing at early GA orfetuses with hydrops. Repeat testing at a later GA yielded conclusiveresults except for one patient. At this time, as most tested patients areundelivered accuracy is determined based on CVS/amniocentesis re-sults with 2% incorrect diagnosis by NIPDT, for example trisomy 18was reported by NIPDT and was normal by FISH and Karyotype.CONCLUSION: The clinical utilization of NIPDT is rapidly expandingwith significant clinical and economical implications. Larger samplesize and independent evaluation of the accuracy of all results in clin-ical setting are clearly required and will be studied by the NIPDTRegistry. Current standard of prenatal diagnosis care should continuealong with critical assessment of the NIPDT results.

596 First trimester screening markers in women withpregestational diabetes mellitus: is a correctionfactor needed?Padmalatha Gurram1, Peter Benn2, Ann-Marie Prabulos1, KistiFuller1, Crawford Christine1, Campbell Winston1

1University of Connecticut, Maternal-Fetal Medicine, Farmington, CT,2University of Connecticut, Clinical Genetics and developmental biology,Farmington, CTOBJECTIVE: To investigate if maternal serum pregnancy associatedplasma protein-A (PAPP-A), total beta hCG and nuchal translu-cency (NT) measurements differ in women with pregestationaldiabetes (PGDM) vs. non-diabetic controls (NDC) and if so is acorrection factor needed for diabetic women.STUDY DESIGN: We performed a retrospective cohort analysis of allwomen having a first trimester aneuploidy screen (11 to 13� 6wks) between 1/2005-12/2011 at our facility. The primary outcomewas difference in PAPP-A, hCG & NT MoM (multiples of the me-dian, corrected for maternal weight, race, gestational age [GA])between PGDM and NDC. Women using insulin (IDDM) or oralhypoglycemics (OHG) prior to pregnancy or at the time of screen-ing were classified as PGDM. Known aneuploidy & multifetal ges-tations were excluded. We also examined if any difference inPAPP-A, hCG and NT between PGDM & NDC is affected by GA orHbA1C.We compared screen positive (1:270)Down syndromerates (DSR) between PGDM & NDC. Chi square & Mann-Whitneytests were used (significant at p �0.05).RESULTS: Of 6741 eligible patients, 103(1.5%) had IDDM & 4(0.06%) were on OHG (excluded due to small number). Outcomeswere available for 1512 patients, of which 67 (4%) developed ges-tational diabetes and were excluded. HbA1C was available for 43IDDM patients. Mean maternal weight in IDDM patients was 202lbs vs. NDC 161 lbs, (p�0.05). There was a 12% reduction ofmedian PAPP-A & 18 % reduction of median total hCG in womenwith IDDM (Table). The effect of IDDM on PAPP-A & hCG didnot differ with GA (p�0.05).The mean HgbA1C% was 7.3�1.5.There was no significant correlation between HbA1C and PAPP-A(Figure), hCG or NT (p �0.05). Screen positive DSR was 8.74% inIDDM vs. NDC 7.19%, (p�0.03).CONCLUSION: In women with IDDM, PAPP-A and hCG were signif-icantly lower compared to NDC and correction factors should beconsidered in the aneuploidy calculation of risks for IDDM pa-tients. This effect is not GA dependent or associated with glycemiccontrol.

Poster Session IV Academic Issues, Antepartum Fetal, Clinical Ob, Fetus, Genetics, Hypertension, Med-Surg-Diseases, Operative Ob, U/S www.AJOG.org

S254 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2013

597 Metabolomic prediction of trisomy 18first trimester pregnanciesRay Bahado-Singh1, Ranjit Akolekar2, Rupsari Mandal3, AnushkaChelliah1, Edison Dong4, Jianguo Xia3, Mike Kruger1, DavidWishart3, Kypros NIcolaides5

1Wayne State University - School of Medicine, Obstetrics and Gynecology,Detroit, MI, 2Medway NHS Foundation Trust, Fetal Medicine Unit,Gillingham, United Kingdom, 3University of Alberta, Biological Sciences,Edmonton, AB, Canada, 4University of Alberta, Computing Sciences,Edmonton, AB, Canada, 5The Fetal Medicine Foundation, Fetal Medicine,London, United KingdomOBJECTIVE: Metabolomics is a rapidly developing field of omics sci-ence that employs a high throughput quantitative approach to char-acterize small molecule metabolites and their metabolism at the sys-tem-wide level.. Our purpose was to determine whether themetabolomic profile is altered in Trisomy 18 (T18) pregnancies andwhether these biomarkers can predict T18.STUDY DESIGN: This was a case control study. NMR based metabolo-mic analyses of maternal serum prospectively collected between 11�0and 13�6 weeks were performed. Metabolite concentrations in 30T18 and 114 euploid controls were compared. Statistical analyses in-cluding logistic regression and genetic programming (GP)[www.Thegmax.com] were performed. Predictive algorithms for T18detection consisting of metabolites by themselves or in combinationwith maternal age and delta nuchal translucency (NT) measure-ments were evaluated.RESULTS: Of a total of 40 metabolites analyzed, 29 had significant dif-ferences in serum concentrations between the groups. Several modelsfor T18 prediction were developed. A logistic model-based on 2-hy-

droxybytrate, formate and maternal age had 56.7% sensitivity and95.6 % specificity for T18 detection, AUC (95% CI); 0.91 (0.86, 0.96),p � 0.001. For 2-hydroxybutyrate plus delta nuchal translucency(NT) these values were 96.7% and 99.1%; AUC (95% CI): 0.99(0.97Using GP analysis, a metabolite only model had 66.7% sensitivityand 99.1% specificity. The addition of NT further improved thesevalues to 93.3% and 98.3 % respectively., 1.000), p � 0.001 respec-tively.CONCLUSION: Conclusion: An extensive group difference in metabo-lomic profile was observed. Metabolomics appears to be a novel toolfor aneuploidy prediction. When combined with NT measurements,preliminary data suggest that high diagnostic accuracy is achievable.

598 The association of �2 adrenoceptor genotype withshort-cervix mediated preterm birthRussell Miller1, Richard Smiley1

1Maternal-Fetal Medicine Units Network, for the Eunice Kennedy ShriverNational Institute of Child Health and Human Development, Bethesda, MDOBJECTIVE: �2 adrenoceptor (�2AR) genotype has been linked to obstet-rical phenotypes. Polymorphic variation encoding for Arg16 homozy-gosity (Arg16Arg) in the transcribed protein is associated with decreasedrisk of preterm labor and preterm delivery (PTD), altered �-agonist re-sponsiveness, and slower rate of active labor. This study was designed todetermine if �2AR genotype is associated with short cervix occurrence orPTD risk following identification of a short cervix.STUDY DESIGN: Nulliparous women with short cervices (length�30mm upon screening sonogram performed between 16-22 weeks)recruited into a multi-center trial were approached to participate.Race-matched women with cervical lengths �40mm were recruited ascontrols (2:1 case:control ratio). Subjects provided blood for DNAisolation. �2AR genotype was determined using primers for polymor-phisms at positions encoding for amino acid residues 16 and 27. Base-line data were collected for all subjects, as well as outcomes data forshort cervix cases. Genotype distributions were compared betweencase and control groups. Within the short cervix group, baseline char-acteristics and outcomes were compared among genotype groups.The primary outcome was PTD �37 weeks. Data were comparedusing chi-squared or Fisher’s exact tests.RESULTS: 444subjectsparticipated, including315cases.Genotypedatawereavailableatposition16for433subjects(2.5%failure),andposition27for437subjects (1.6% failure). Expected Hardy-Weinberg equilibrium existed atboth positions. There was no difference in frequency of Arg16Arg (22.4% vs25.0%, p�0.56) or Gln27 homozygosity (Gln27Gln, 8.0% vs 7.3%, p�0.82)between cases and controls. Among cases, Arg16Arg had no effect on PTDnor spontaneous PTD (table). Gln27Gln had no effect on PTD, althoughsample size for this analysis was limited.CONCLUSION: �2AR genotype is not associated with short cervix oc-currence or PTD after a short cervix diagnosis. Putative protectionfrom PTD associated with Arg16Arg does not involve short cervixpathways.

Scatter plot showing maternal serumPAPP-A MoM versus HbA1c values

First-trimester screening markerdifferences in IDDM compared to NDC

1 P value less than 0.05 is considered to be significant.

�2AR genotype and preterm delivery insubjects with short cervix

1. PTD, preterm delivery.

www.AJOG.org Academic Issues, Antepartum Fetal, Clinical Ob, Fetus, Genetics, Hypertension, Med-Surg-Diseases, Operative Ob, U/S Poster Session IV

Supplement to JANUARY 2013 American Journal of Obstetrics & Gynecology S255