730: Impact of increased utilization of early aneuploidy screening on genetic amniocenteses...

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RESULTS: 3 of the 105 pregnancies tested positive; all three involved Noonan syndrome (PTPN11 [2]; RAF-1). There were no pregnancies identified with DiGeorge syndrome, congenital adrenal hyperplasia, Smith-Lemli-Opitz syndrome and spinal muscle atrophy. CONCLUSIONS: With the exception of Noonan syndrome, the fre- quency of association of increased NT and developmental/genetic syndromes, as listed by Souka et al. (2005) and Bilardo et al. (2010), remains unresolved in terms of their true clinical significance. Reflex testing for cardiac abnormalities and Noonan Syndrome seems war- ranted with enlarged NT and normal karyotype. Further data are re- quired to determine the utility of looking for other genetic syndromes. 729 Performance adjusted risks (par) for optimization of laboratory analytes Mark Evans 1 , Howard Cuckle 2 1 Comprehensive Genetics & Mt. Sinai School of Medicine, New York, NY, 2 Columbia University, New York, NY OBJECTIVE: Variability of performance among providers is a serious quality concern for screening. We created PAR, assigning “handicaps” to individual’s distributions of data for US measurements such as NT’s, which raises or lowers the contribution of provider’s values in algorithmic determination of risk assessment. NT performance was improved by about 2%. Here, we extend PAR to laboratory analytes by their distributions. STUDY DESIGN: Data were analyzed from 7255 women, (median age 36 at delivery), including 32 DS cases and 18 other aneuploidies, who had first trimester free â-hCG and PAPP-A determinations. Measure- ments were converted into MoMs using locally derived equations. Experimentally to simulate poor performance, the free â-hCG levels were decreased by 10% and PAPP-A levels increased by 10%. PAR was calculated as the maximum absolute percentage deviation of the LR in unaffected pregnancies based on the altered means from the LR using standard software, over the range 0.3-5.0 MoM for free â-hCG and 0.2-3.0 MoM for PAPP-A. The detection rate (DR) was calculated for the two biochemical markers, using a 1/250 term risk cut-off, without PAR and after handicapping risks with PAR to downplay poor per- formance and increase quality performance. RESULTS: PAR was calculated to be 150%. The DR without PAR was 69%; with PAR, DR rose to 72%. For other aneuploidies: 33% and 39%. DR for a fixed 5% false-positive rate were 59% and 62%. CONCLUSIONS: 1. As with NT data, PAR values can improve screening performance by raising or lowering the contribution of parameters in an algorithm as a function of the quality of the measurements. 2. The contribution of poor sonographers’ NT’s values is minimized, 3. Lab- oratory measurements’ contributions vary with coefficient of varia- tion. 4. Use of PAR for both laboratory and ultrasound measurements in algorithms can improve the efficacy of screening programs by about 2-4% which can have enormous economic implications - potentially saving tens of millions of dollars per year in the USA. 730 Impact of increased utilization of early aneuploidy screening on genetic amniocenteses available for maternal fetal medicine (MFM) fellowship training Nancy Rose 1 , Danielle LaGrave 2 , Brent Hafen 1 , Marc Jackson 1 1 Intermountain Healthcare, Salt Lake City, UT, 2 ARUP Laboratories, Salt Lake City, UT OBJECTIVE: Newer methods of aneuploidy screening (first and second trimester serum analytes combined with nuchal translucency mea- surement), have high detection rates and low false positive rates. These test options became clinically available for our population in 2004. This report describes the effect that introduction of these early screening methods has had on the number of genetic amniocentesis procedures available for MFM fellowship training. STUDY DESIGN: Descriptive study of referrals for aneuploidy screening and invasive genetic testing in an academic MFM setting. Data from 2003-2009 from three tertiary centers where MFM fellows have access to procedures were analyzed. All genetic amniocenteses and screening tests utilizing nuchal translucency measurements were evaluated; quad and triple screening were excluded. Screening data were ob- tained from the regional laboratory that is responsible for nearly all genetic testing in our region. RESULTS: Utilization of non-invasive early screening methods in- creased from 0 to 1202 between 2004-2009. The percentage of screen- ing patients who were age 35 or older increased from 12.7% to 35.4% between 2005- 2009. The number of amniocenteses declined from 632 to 327 (-48.3%) between 2003-2009. The average annual number of amniocenteses declined from 673 in 2000-2003 to 368 in 2007-2009 (- 45.2%). CONCLUSIONS: The utilization of early screening for aneuploidy has substantially increased in our population since its introduction, even among women older than 35 years. This has led to a 45% decline in genetic amniocentesis procedures available. This effect may be more pronounced with future implementation of aneuploidy screening via free fetal nucleic acids in maternal blood. MFM fellowship programs should evaluate their experience to be certain that fellows are skilled in counseling for early aneuploidy screening and that adequate training methods for prenatal diagnostic procedures are available. 731 Specific gene expression in the placenta of a mouse model lacking endothelial nitric oxide synthase Ramzy Nakad 1 , Maged Costantine 1 , Talar Kechichian 1 , Huaizhi Yin 1 , Gary D.V. Hankins 1 , George R. Saade 1 , Monica Longo 1 1 The University of Texas Medical Branch, Galveston, TX OBJECTIVE: We have previously shown that the abnormal intrauterine environment in mice lacking the endothelial nitric oxide synthase (NOS3) leads to hypertension and abnormal vascular function in the adult offspring. NOS3, vascular endotelial growth factor receptor- 1(VEGF-R1) and tumor necrosis factor-á (TNFá) are known to play a role in utero-placental perfusion, angiogenesis and inflammation. Our objective was to evaluate their involvement in the altered fetal programming of adult vascular function in this transgenic model of utero-placental insufficiency. STUDY DESIGN: Male and female homozygous NOS3 knockout (KO) and wild-type mice (WT) were cross-bred to obtain KO and WT lit- ters, as well as genomically-similar heterozygous litters developing in either a normal (paternally-derived; KOP) or abnormal (maternally- derived; KOM) uterine environment. The dams were sacrificed at day 18 of gestation, and the placentas were harvested.and homogenized. Proteins were extracted for Western blot analysis normalized to â- actin. One-way ANOVA was used for statistical analysis (significance: P 0.05). RESULTS: TNFá protein expression was similar between the 4 groups. VEGF-R1 expression was decreased in placentas of KO pups com- pared with placentas from KOM, KOP or WT pups (69.68.1; www.AJOG.org Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging Poster Session V Supplement to JANUARY 2011 American Journal of Obstetrics & Gynecology S287

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www.AJOG.org Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging Poster Session V

RESULTS: 3 of the 105 pregnancies tested positive; all three involvedoonan syndrome (PTPN11 [2]; RAF-1). There were no pregnancies

dentified with DiGeorge syndrome, congenital adrenal hyperplasia,mith-Lemli-Opitz syndrome and spinal muscle atrophy.

CONCLUSIONS: With the exception of Noonan syndrome, the fre-uency of association of increased NT and developmental/geneticyndromes, as listed by Souka et al. (2005) and Bilardo et al. (2010),emains unresolved in terms of their true clinical significance. Reflexesting for cardiac abnormalities and Noonan Syndrome seems war-anted with enlarged NT and normal karyotype. Further data are re-uired to determine the utility of looking for other genetic syndromes.

729 Performance adjusted risks (par)or optimization of laboratory analytes

Mark Evans1, Howard Cuckle2

1Comprehensive Genetics & Mt. Sinai School of Medicine,ew York, NY, 2Columbia University, New York, NY

OBJECTIVE: Variability of performance among providers is a seriousuality concern for screening. We created PAR, assigning “handicaps”o individual’s distributions of data for US measurements such asT’s, which raises or lowers the contribution of provider’s values in

lgorithmic determination of risk assessment. NT performance wasmproved by about 2%. Here, we extend PAR to laboratory analytes byheir distributions.

STUDY DESIGN: Data were analyzed from 7255 women, (median age 36t delivery), including 32 DS cases and 18 other aneuploidies, who hadrst trimester free â-hCG and PAPP-A determinations. Measure-ents were converted into MoMs using locally derived equations.

xperimentally to simulate poor performance, the free â-hCG levelsere decreased by 10% and PAPP-A levels increased by 10%. PAR was

alculated as the maximum absolute percentage deviation of the LR innaffected pregnancies based on the altered means from the LR usingtandard software, over the range 0.3-5.0 MoM for free â-hCG and.2-3.0 MoM for PAPP-A. The detection rate (DR) was calculated forhe two biochemical markers, using a 1/250 term risk cut-off, withoutAR and after handicapping risks with PAR to downplay poor per-

ormance and increase quality performance.RESULTS: PAR was calculated to be 150%. The DR without PAR was

9%; with PAR, DR rose to 72%. For other aneuploidies: 33% and9%. DR for a fixed 5% false-positive rate were 59% and 62%.

CONCLUSIONS: 1. As with NT data, PAR values can improve screeningerformance by raising or lowering the contribution of parameters inn algorithm as a function of the quality of the measurements. 2. Theontribution of poor sonographers’ NT’s values is minimized, 3. Lab-ratory measurements’ contributions vary with coefficient of varia-ion. 4. Use of PAR for both laboratory and ultrasound measurementsn algorithms can improve the efficacy of screening programs by about-4% which can have enormous economic implications - potentiallyaving tens of millions of dollars per year in the USA.

730 Impact of increased utilization of early aneuploidycreening on genetic amniocenteses available foraternal fetal medicine (MFM) fellowship training

Nancy Rose1, Danielle LaGrave2, Brent Hafen1, Marc Jackson1

1Intermountain Healthcare, Salt Lake City, UT,2ARUP Laboratories, Salt Lake City, UTOBJECTIVE: Newer methods of aneuploidy screening (first and secondrimester serum analytes combined with nuchal translucency mea-urement), have high detection rates and low false positive rates.hese test options became clinically available for our population in004. This report describes the effect that introduction of these earlycreening methods has had on the number of genetic amniocentesisrocedures available for MFM fellowship training.

STUDY DESIGN: Descriptive study of referrals for aneuploidy screeningand invasive genetic testing in an academic MFM setting. Data from2003-2009 from three tertiary centers where MFM fellows have access

to procedures were analyzed. All genetic amniocenteses and screening p

Supplem

tests utilizing nuchal translucency measurements were evaluated;quad and triple screening were excluded. Screening data were ob-tained from the regional laboratory that is responsible for nearly allgenetic testing in our region.RESULTS: Utilization of non-invasive early screening methods in-reased from 0 to 1202 between 2004-2009. The percentage of screen-ng patients who were age 35 or older increased from 12.7% to 35.4%etween 2005- 2009. The number of amniocenteses declined from 632o 327 (-48.3%) between 2003-2009. The average annual number ofmniocenteses declined from 673 in 2000-2003 to 368 in 2007-2009 (-5.2%).

CONCLUSIONS: The utilization of early screening for aneuploidy hasubstantially increased in our population since its introduction, evenmong women older than 35 years. This has led to a 45% decline inenetic amniocentesis procedures available. This effect may be moreronounced with future implementation of aneuploidy screening via

ree fetal nucleic acids in maternal blood. MFM fellowship programshould evaluate their experience to be certain that fellows are skilled inounseling for early aneuploidy screening and that adequate trainingethods for prenatal diagnostic procedures are available.

731 Specific gene expression in the placenta of a mouseodel lacking endothelial nitric oxide synthase

Ramzy Nakad1, Maged Costantine1, Talar Kechichian1, Huaizhiin1, Gary D.V. Hankins1, George R. Saade1, Monica Longo1

1The University of Texas Medical Branch, Galveston, TXOBJECTIVE: We have previously shown that the abnormal intrauterinenvironment in mice lacking the endothelial nitric oxide synthaseNOS3) leads to hypertension and abnormal vascular function in thedult offspring. NOS3, vascular endotelial growth factor receptor-(VEGF-R1) and tumor necrosis factor-á (TNFá) are known to play aole in utero-placental perfusion, angiogenesis and inflammation.ur objective was to evaluate their involvement in the altered fetalrogramming of adult vascular function in this transgenic model oftero-placental insufficiency.

STUDY DESIGN: Male and female homozygous NOS3 knockout (KO)nd wild-type mice (WT) were cross-bred to obtain KO and WT lit-ers, as well as genomically-similar heterozygous litters developing inither a normal (paternally-derived; KOP) or abnormal (maternally-erived; KOM) uterine environment. The dams were sacrificed at day8 of gestation, and the placentas were harvested.and homogenized.roteins were extracted for Western blot analysis normalized to â-ctin. One-way ANOVA was used for statistical analysis (significance:� 0.05).

RESULTS: TNFá protein expression was similar between the 4 groups.EGF-R1 expression was decreased in placentas of KO pups com-

ared with placentas from KOM, KOP or WT pups (69.6�8.1;

ent to JANUARY 2011 American Journal of Obstetrics & Gynecology S287