32 THE ROLE OF GENOME DAMAGE AND FOLATE NUTRIGENOMICS IN UTEROPLA-CENTAL INSUFFICIENCY (UPI) DENISE FURNESS1, GUSTAAF DEKKER2,YEE KHONG3, BILL HAGUE4, MICHAEL FENECH5, 1Csiro Adelaide BC, South Aus-tralia, Australia, 2Women’s and Children’s Hospital, Obstetrics and Gynaecol-ogy, North Adelaide, South Australia, Australia, 3Women’s and Children’sHospital, Adelaide, Obstetrics and Gynaecology, North Adelaide, SouthAustralia, Australia, 4Women’s and Children’s Hospital, Adelaide, NorthAdelaide, South Australia, Australia, 5CSIRO, Human Nutrition, Adelaide,South Australia, Australia

OBJECTIVE: To study genome damage markers and maternal plasmaconcentrations of micronutrients and homocysteine in women with UPI.

STUDY DESIGN: Prospective observational study. Methods: Genome dam-age (micronuclei, nucleoplasmic bridges, nuclear buds) and cytotoxicity (apo-ptosis, necrosis, nuclear division index) markers in peripheral bloodlymphocytes using the cytokenesis block micronucleus assay together withplasma concentrations of micronutrients – folate, vitamin B12 and vitamin B6 –and homocysteine, were evaluated at 20 weeks gestation in 53 healthy pregnantwomen with normal outcomes and in 90 women with high risk pregnancies.

UPI was defined as preeclampsia or gestational hypertension, and/orintrauterine growth restriction (IUGR) !10th centile and/or placental abrup-tion. Comparisons of differences in the genome damage markers and plasmaconcentrations of micronutrients and homocysteine were made between datafrom pregnancies with healthy outcomes and data from pregnancies compli-cated by UPI using ANOVA.

RESULTS: Micronucleus frequency (%0) was significantly increased in UPI,controls 18.27 C/� 0.85, UPI 23.99 C/�1.80 (P=0.002). There wereno differences in micronutrient concentrations between groups. Plasmahomocysteine was also increased in UPI, controls 4.24G0.11 mol/L, UPI5.19 G 0.25 mol/L (P ! 0.0001).

CONCLUSION: Our study supports the hypothesis thatmicronucleus frequencyO35%0 in peripheral blood lymphocytes and homocysteine O6.5 mol/L at 20weeks gestation have significant predictive value for the development of UPI.

Table 1: Positive predictive values (PPV), Negative predictive values (NPV),

Likelihood ratio (LR), Sensitivity, Specificity for micronucleus (MN) fre-

quency and plasma homocysteine (Hcy) shown in table 1 indicate the relative

potential for these biomarker

PPV% NPV% LR Sensitivity% Specificity%

S14 SMFM Abstracts

30 TRENDS IN STATE/POPULATION-BASED DOWN SYNDROME (DS) SCREENING ANDINVASIVE PRENATAL TESTING WITH THE INTRODUCTION OF FIRST TRIMESTERCOMBINED DS SCREENING, SOUTH AUSTRALIA 1995-2004 PETER MULLER1,CHRIS WILKINSON1, ROBERT COCCIOLONE2, RHONDA HUTCHINSON2,ERIC HAAN3, ANNABELLE CHAN4, 1Women’s and Children’s Hospital, PerinatalMedicine, North Adelaide, South Australia, Australia, 2Women’s and Child-ren’s Hospital, Genetic Medicine, North Adelaide, South Australia, Australia,3Women’s and Children’s Hospital, Department of Genetic Medicine, Ade-laide, South Australia, Australia, 4Department of Health, Pregnancy OutcomeUnit, Adelaide, South Australia, Australia

OBJECTIVE: A state–based first trimester combined DS screening programwas introduced in South Australia (population 1.54 million) in 2000. Wereviewed trends in utilization of maternal serum DS screening and invasiveprenatal testing (CVS and amniocentesis) before and after the introduction ofthis program.

STUDY DESIGN: A retrospective population-based study was performed onthe utilization of DS screening and prenatal invasive testing in South Australiafrom the South Australian Birth Defects Register and the Department ofCytogenetics at the Women’s and Children’s Hospital (South Australia’s solecytogenetics laboratory)from 1995 to 2004. Chi-square tests were used toevaluate trends in utilization of first and second trimester DS screening andinvasive prenatal testing.

RESULTS: There was an average of 18,031 confinements per year from1995-2004. During this period, there was a significant decrease in secondtrimester DS screening from 75% of confinements in 1995 to 28% in 2004(p!0.0001), and a significant increase in first trimester combined screening,0.8% in 2000 to 44% in 2004 (p!0.0001). Despite a significant increase in theproportion of confinements with maternal age O= 35, 12.5% in 1995 to17.9% in 2004 (p!0.0001), this age group underwent less invasive prenataltesting, 43% in 1995 to 27.4% in 2004 (p!0.0001) and the rate of totalinvasive testing also fell in the state, 9.3% in 1995 to 7.9% in 2004 (p!0.0001).There was a significant decrease in the number of invasive prenatal tests todetect one aneuploidy fetus from 1:39 in 1995 to 1:23 in 2004 (p!0.001).

CONCLUSION: The introduction and increase in utilization of first trimestercombined DS screening has been associated with more effective utilization ofinvasive prenatal testing in South Australia.

0002-9378/$ - see front matterdoi:10.1016/j.ajog.2006.10.036

31 FIRST-TRIMESTER RISK ASSESSMENT FOR TRISOMY 21 AND 18 IN TWINPREGNANCY STEPHEN CHASEN1, SRIRAM PERNI1, ROBIN B. KALISH1, FRANKA. CHERVENAK1, 1Weill Medical College of Cornell University, New York,New York

OBJECTIVE: Our objective was to describe performance of first-trimestercombined risk assessment in twin pregnancies.

STUDY DESIGN: Twin pregnancies undergoing risk assessment in ourultrasound unit from 2003-2005 were included. Nuchal translucency (NT)was measured from 11-14 weeks (CRL 45-84mm). PAPP-A and free b-hCGwere measured from 9-14 weeks. Adjusted risks for T21 and T18 based on age,NT, and biochemistry were provided for each twin. Abnormal karyotypeswere identified from CVS and amniocentesis in those undergoing prenataldiagnosis; products of conception following spontaneous or elective abortion;or from postnatal testing if indicated. Detection rates for T21 and T18 werecalculated for age/NT, and age/NT/biochemistry at a screen-positive rate of5% of pregnancies. For each pregnancy, the higher adjusted risk of T21 andT18 of the two fetuses was used to calculate screening performance.

RESULTS: 471 pregnancies were included. Median maternal age was 34years, with 47% of women R35. There were 4 fetuses with T21 and 3 with T18in 7 dizygotic pregnancies. Detection rates of T21 and T18 for screen-positiverates of 5% are seen in the table. Using a cutoff of 1 in 270, all 4 cases of T21would be detected with both age/NT and age/NT/Biocehmistry, with false-positive rates of 11.5% and 7.6%, respectively.

CONCLUSION: Many women with multifetal pregnancies are older and haveexperienced infertility. These patients may be reluctant to undergo invasivetesting. Based on our data, risk assessment for T21 and T18 in twins using NT/biochemistry is superior to using age alone or age/NT. We noted highdetection rates with screen-positive rates of 5%. When available, first-trimestercombined risk assessment should be offered to women with twin pregnancies.

Trisomy 21/18 Detection with 5% Screen Positive Rate

T21:Age

T21:Age/NT

T21: Age/NT/Blood T18: Age

T18:Age/NT

T18: Age/NT/Blood

Cutoff 41years

1 in 121 1 in 192 41 years 1 in 234 1 in 1573

Detection 25%(1/4)

75%(3/4)

100%(4/4)

33.3%(1/3)

66.7%(2/3)

100%(3/3)

0002-9378/$ - see front matterdoi:10.1016/j.ajog.2006.10.037

0002-9378/$ - see front matterdoi:10.1016/j.ajog.2006.10.038

33 GENES IN GLUCOSE METABOLISM AND THEIR ASSOCIATION WITH SPINA BIFIDACHRISTINA DAVIDSON1, HOPE NORTHRUP2, TERRI KING2, JACK FLETCHER3,IRENE TOWNSEND3, GAYLE TYERMAN4, KIT SING AU2, 1University of Texas HealthScience Center at Houston, Obstetrics, Gynecology and ReproductiveSciences, Houston, Texas, 2University of Texas Health Science Center atHouston, Pediatrics and Medical Genetics, Houston, Texas, 3University ofHouston-Texas Medical Center Annex, Psychology, Houston, Texas,4Shriners Hospitals for Children, Los Angeles, California

OBJECTIVE: Neural tube defects (NTDs) are known to be a result ofenvironmental factors and genetic predisposition. Maternal diabetes with poorglucose control during pregnancy is a risk factor for NTDs. Evidence suggeststhat the underlying mechanism is elevated glucose levels in the mother duringembryogenesis. Our objective was to test polymorphic variants in codingsequences of candidate genes selected from the glucose metabolism pathway todetermine if any single nucleotide polymorphism (SNP) confers an increasedsusceptibility to spina bifida (SB).

STUDY DESIGN: Our affected population consisted of 610 children with SB.Blood samples were obtained from the patients and their parents and genomicDNA was extracted. In addition, anonymous control DNAs from 92 Hispanicand 92 Caucasian individuals without a personal or family history of NTDswere obtained. We investigated SNPs located in the coding region of 13candidate genes that are involved in glucose metabolism and diabetes to testtheir association in the etiology of SB. These genes were INS, INSR, HK1,HK2, SOD1, SOD2, LEP, LEPR, CAT, GLUT1, GLUT4, TP53 and GAPD.SNP genotyping was carried out using a high throughput SNPlex genotypingplatform based on multiplex-oligonucleotide ligation/PCR assay. For trioanalysis, the standard transmission disequilibrium test (STDT) and recon-struction-combined TDT were performed to test for genetic associationsbetween transmission of alleles and SB in the offspring. A p-value of less than0.05 was considered statistically significant.

RESULTS: A statistically significant association between K481 of HK1 (Gallele), R109K of LEPR (G allele) and P196 of GLUT1 (A allele) was found(p=0.019, 0.035 and 0.040, respectively). The case populations were in Hardy-Weinberg equilibrium. The TDT tests showed no statistical significances forthe remaining 10 candidate genes studied.

CONCLUSION: Three SNPs on 3 genes involved with glucose metabolismare associated with increased susceptibility to SB.

0002-9378/$ - see front matterdoi:10.1016/j.ajog.2006.10.039

MN O 35 %0 77 62 4.5 22 95Hcy O6.5 56 60 2.7 20 89MN O 35 %0 C Hcy O6.5 25 90 2.7 28 89