567 MOM VERSUS DELTA NT: TRISOMY-21 RISK ASSESSMENT USING NUCHALTRANSLUCENCY (NT) SONOGRAPHY FERGAL D. MALONE1, HOWARD CUCKLE2,ROBERT H. BALL3, DAVID A. NYBERG4, CHRISTINE H. COMSTOCK5, RADEKBUKOWSKI6, KEITH EDDLEMAN7, SUSAN J. GROSS8, LORRAINE DUGOFF9, SABRINAD. CRAIGO10, ILAN E. TIMOR11, STEPHEN R. CARR12, HONOR M. WOLFE13, KIM-BERLY A. DUKES14, MARY E. D’ALTON15, 1Royal College of Surgeons in Ireland,Dublin, Ireland, 2University of Leeds, Leeds, United Kingdom, 3Universityof Utah, Salt Lake City, Utah, 4Swedish Medical Center, Seattle, Washington,5William Beaumont Hospital, Royal Oak, Michigan, 6University of TexasMedical Branch at Galveston, Galveston, Texas, 7Mount Sinai School of Med-icine, New York, New York, 8Albert Einstein College of Medicine, Bronx,New York, 9University of Colorado Health Sciences Center, Denver, Colo-rado, 10Tufts University, Boston, Massachusetts, 11NYU Medical Center,New York, New York, 12Brown University, Providence, Rhode Island, 13Uni-versity of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 14DM-STAT, Boston, Massachusetts, 15Columbia University, New York, New York

OBJECTIVE: To compare the two most commonly used approaches forinterpretation of nuchal translucency (NT) sonography for Trisomy-21 riskassessment: multiples of the median (MoM) and Delta NT (NT).

STUDY DESIGN: 35,087 patients had NT at 11-13 wks, including 116 casesof Trisomy-21. NT measurements were converted to both MoM and NT. NTMoMs were used with Gaussian likelihood ratios (LRs), and NTs were usedwith empirical LRs from a large prospective study (Spencer et al, UltrasoundObstet Gynecol, 2003;22:142), to generate individualized patient risk estimatesfor Trisomy-21. A 1:270 mid-trimester risk cut-off was used to define screenpositivity.

RESULTS: NT distribution in unaffected pregnancies was not constant, withinter-tertile ranges of 0.67, 0.75 and 0.83 mm at 11, 12 and 13 wks respectively.The sensitivity of NT with maternal age using NT and empirical LRs was 66%(3.1% FPR), compared with 78% (8.2% FPR) when using NT MoM andGaussian LRs. At a fixed 5% FPR, detection rates were 71% and 72%respectively. The observed prevalence of Trisomy-21 was closer to thatexpected from NT MoM-based risks than with the NT approach (see Table).

CONCLUSION: Calculating individualized patient risk for Trisomy-21 usingNT MoMs is superior to use of NT, with more cases detected, and moreaccurate risk estimates. (NIH-RO1-HD-38652)

Risk MoM Delta NT(1 in) N Expected (%) Observed (%) N Expected (%) Observed (%)

O25 449 15.0 12.0 179 13.2 22.425-50 228 2.9 4.8 148 2.9 7.451-100 347 1.4 2.6 173 1.4 5.8101-200 746 0.7 1.2 306 0.7 2.6201-400 1,605 0.3 0.6 442 0.3 2.0401-800 3,124 0.2 0.3 874 0.2 0.8!800 28,588 0.04 0.06 32,965 0.01 0.09All 35,087 0.30 0.21 35,087 0.12 0.21

568 D331(GOA) POLYMORPHISM IN PROGESTERONE RECEPTOR GENE IS NOTASSOCIATED WITH SPONTANEOUS PRETERM BIRTH ERROL NORWITZ1, THOMASMORGAN2, VICTORIA SNEGOVSKIKH1, JESSICA ILLUZZI1, CATALIN BUHIMSCHI1,IRINA BUHIMSCHI1, EDMUND FUNAI1, EDWARD KUCZYNSKI1, CHARLESLOCKWOOD1, 1Yale University, Obstetrics & Gynecology, New Haven, Con-necticut, 2Yale University, Genetics, New Haven, Connecticut

OBJECTIVE: Progesterone supplementation can prevent preterm birth insome high-risk women. Progesterone acts by binding to progesterone receptors(PR) and modulating the expression of target genes. Single nucleotidepolymorphisms (SNPs) in the single-copy human PR gene have been associ-ated with recurrent miscarriage and reproductive tract malignancies. Thisstudy investigates for the first time the association between C331(GOA) SNPin the PR gene and preterm birth. This SNP alters the ratio of PR-A to PR-Bisoforms in myometrium, which has been shown to change prior to the onsetof labor.

STUDY DESIGN: Consecutive patients with spontaneous (non-iatrogenic)preterm birth were identified from the March of Dimes Perinatal EmphasisResearch Initiative project (MOD # 20-FY03-30) at New York University, NYand Yale-New Haven Hospital, CT, Jan 1989-June 2005. Cases were matched(1:3) with uncomplicated term deliveries (controls). DNA was extracted fromstored buffy coats and genotyped for C331 (GOA) SNP using establishedprimers. All specimens were linked with demographic and medical dataabstrated from maternal/neonatal records. Chi-squares and logistic regressionwere used to evaluate the relationship between race/ethnicity, genotype, andpreterm birth.

RESULTS: 72/77 (94%) of cases and 230/234 (98%) of controls weresuccessfully genotyped. The rate of C331 (GOA) SNP heterozygous state inpreterm birth cases was 4.2% (3/72) vs 4.8% (11/230) in controls (OR, 0.87;95% CI, 0.24-3.19); no homozygotes were identified. The heterozygous statewas found in 9.5% (2/21) of Caucasians, 5.4% (9/167) of Hispanics, and 5%(3/60) of others; no carriers were found among Asian (0/34) or African-American (0/20) women (P=0.407). Logistic regression analysis failed to showany interaction between race/ethnicity and C331 (GOA) SNP genotype inpredicting preterm birth (P=0.974).

CONCLUSION: The C331 (GOA) SNP in human PR gene does not appearto be associated with spontaneous preterm birth. Further studies are requiredto define the mechanism by which progesterone supplementation preventspreterm birth.

569 EVALUATION OF THE SIGNIFICANCE OF A POSITIVE SERUM SCREEN FOR TRISOMY18 YINKA OYELESE (F)1, LUIS TOBON1, JOSEPH CANTERINO2, CANDE ANANTH1,MARTIN CHAVEZ1, LAMI YEO1, JOHN SMULIAN1, ANTHONY VINTZILEOS1,1UMDNJ-Robert Wood Johnson Medical School/Robert Wood JohnsonUniversity Hospital, Obstetrics, Gynecology, and Reproductive Sciences,New Brunswick, New Jersey, 2Perinatal Institute, Jersey Shore Medical Cen-ter, Obstetrics & Gynecology, Neptune, New Jersey

OBJECTIVE: 1. To evaluate the proportion of false positive (FP) serumscreens (SS) for Trisomy 18 (T18). 2. To determine the proportion of falsenegative (FN) serum screens for T18. 3. To evaluate the sensitivity ofultrasound for diagnosing T18. 4. To determine if FP SS for T18 wereassociated with other pregnancy complications.

STUDY DESIGN: This was a retrospective cohort study of women with apositive SS for T18 at our institutions. Cases were ascertained through theultrasound database using the diagnoses ‘‘positive SS for T18’’ and ‘‘T18’’. Wecalculated the proportions of FP SS and the positive predictive value (PPV) ofSS for T18. We also evaluated the proportion of FN SS in women who hadpregnancies with T18. We evaluated the sensitivity of ultrasound for diagnos-ing T18. Finally, we recorded whether pregnancies associated with a FP SS forT18 had any other pregnancy complications.

RESULTS: There were 93 women with positive SS for T18 with a range ofreported risks for T18 ranging from 1:2 to 1:100. There were 8 cases of T18.Only 3 women with a positive SS for T18 had fetuses with T18. The proportionof FP SS was 97%, while the PPV of the T18 SS was 3.2%. There were 3/6cases of T18 with a negative SS, giving a proportion of FN of 50%. Two casesof T18 had no SS. In all cases of T18, ultrasound demonstrated multiplemajor structural anomalies (Miminum of 4). Thus ultrasound had a 100%sensitivity for T18. Ten pregnancies (11%) with FP SS for T18 had other fetalanomalies.

CONCLUSION: Patients with positive SS for T18 have a low likelihood ofhaving fetuses with T18. In the absence of structural anomalies on ultrasoundin experienced hands, a diagnosis of T18 is very unlikely. Thus women with apositive SS for T18 who have a normal ultrasound should be counseled thatthe risk of losing a normal fetus from the amniocentesis exceeds the likelihoodof detecting a T18 fetus. This strategy will reduce costs and unnecessarypregnancy losses associated with amniocentesis. However, the high rate ofother anomalies justifies a thorough sonographic anatomic survey in thesewomen.

570 TRENDS IN AMNIOCENTESIS UTILIZATION FROM 1990 TO 2002 HENRY ROQUE1,BRUCE MORRIS1, MARY BETH JANICKI1, JAMES EGAN1, 1University of Connecti-cut, Obstetrics and Gynecology, Farmington, Connecticut

OBJECTIVE: To assess trends in amniocentesis utilization and its relation tothe incidence of Down Syndrome (DS) livebirths in the United States from1990 to 2002.

STUDY DESIGN: Non-diabetic patients from the Natality Data Set from theyears 1990 to 2002 were evaluated for documentation of amniocentesis andstratified by maternal age . Diabetic patients were excluded to decrease asource of non-genetic amniocentesis. We modeled the Natality data for theestimates of expected Down syndrome (DS) births and recorded maternal agespecific prevalence of DS livebirths.

RESULTS: A total of 49,483,175 non-diabetic pregnancies were analyzed. Inthe study interval a 47.6% & 45% reduction in the percent of pregnancies witha recorded amniocentesis was observed in women O35 yrs and !35 yrsrespectively. During this interval there was an increase in the prevalence oflivebirths to women O35 yrs from 9.2% to 14.9%. Modeling the Natality dataon estimates of expected Down syndrome (DS) births there is an anticipatedincrease of 540% in the incidence of DS for women !35 yrs, and a 359%increase for women O35 yrs. Yet during this time there was no change in thetotal number of reported DS livebirths (1863 in 1990 vs 1738 in 2002).

Percent of pregnancies with a recorded amniocentesis

CONCLUSION: Despite the observed decrease in amniocentesis there was adecrease in the observed/expected DS livebirths. These findings taken togethersuggest wide acceptance of non-invasive DS screening strategies, or anincreased acceptance of Chorionic villus sampling.

S162 SMFM Abstracts