718: why do women decline genetic amniocentesis?

1
STUDY DESIGN: 62 candidate genes for obligate twinning were identi- fied, including members of the Bone Morphogenetic Protein (BMP), Growth and Differentiation Factor (GDF), and IGF gene families and pathways. Marmoset specific nonsynonymous (meaning resulting in an amino acid change) substitutions (NS) were identified using the 33-way eutherian mammal EPO alignments from Ensembl. These NS substitutions were compared, and only marmoset NS conserved among all other haplorhines were retained. NS with a probable effect on protein function were identified using SIFT. In extensive valida- tions studies, exon amplicons of these NS were sequenced in 7 cal- litrichid and 3 non-callitrichid NWM species. RESULTS: 22 callitrichid-specific and validated NS were present in only 14 genes (Table). Of interest, GDF9 and BMP15 variants have previ- ously been observed in sheep breeds which twin. The BMP15 NS is a valine to threonine conversion in the signal peptide. Two NS in GDF9 occur in the propeptide, and include an asparagine to serine change that disrupts glycosolyation. CONCLUSION: We have identified and validated callitrichid specific NS that likely yield obligate twinning. Further characterization of these NS will provide candidate regions for examination of human single nucleotide polymorphisms that may have implications in twinning, and emphasize the discovery potential of primate comparative genomics for human perinatal disorders. 718 Why do women decline genetic amniocentesis? Douglas Richards 1 , Lorna Rodriguez 2 , Melanie Adamsky 3 , Katherine Davidson 3 1 Intermountain Medical Center and the University of Utah, Maternal Fetal Medicine, Murray, UT, 2 University of Florida, Maternal Fetal Medicine, Gainesville, FL, 3 University of Florida, Obstetrics and Gynecology, Gainesville, FL OBJECTIVE: There has been a well-recognized decrease in the number of women undergoing invasive genetic diagnosis. The purpose of this study is to discover reasons that women decline testing. STUDY DESIGN: 3779 women having second trimester genetic counsel- ing between 10/2004 and 5/2010 at the University of Florida in Gainesville were offered amniocentesis. Following the counseling ses- sion, patients intention to have amniocentesis was recorded by the genetic counselor. After ultrasound evaluation, those who declined the procedure were asked to complete a simple questionnaire stating their reasons for refusal. Regression analysis was used to determine associations between reasons for refusal and demographic factors, in- cluding age, parity, race/ethnicity, marital status and urban or rural place of residence. RESULTS: At the conclusion of the counseling session, 70% of patients had decided whether they wanted amniocentesis. Of these, 75% de- clined. 30% patients were undecided, wanting to see if the ultrasound was OK before committing. Only 12% of these ultimately chose am- niocentesis. Of those who declined, for whom post-ultrasound ques- tionnaires were available, roughly two thirds chose worry about risks (risks), feeling reassured by non-invasive testing (reassured), and abortion not being an option (no abortion) as reasons. 94% of declin- ers had more than one reason. No demographic factors were associ- ated with risks, or reassured. Ethnicity was strongly associated with no abortion as a reason (p0.002); cited by 57 of 103 (45%) of blacks and 59 of 110 (46%) of Hispanics, but only 340 of 534 (36%) of whites. Rural residency (p0.004) and younger age (p.02) were also asso- ciated with no abortion as a reason. CONCLUSION: Many patients use ultrasound findings to help them de- cide to have amniocentesis. Of undecided patients, the majority de- cline. Fear of complications, feeling reassured by non-invasive tests, and no abortion are cited roughly equally as reasons. Black or His- panic ethnicity, rural residence, and younger age are associated with no abortion as an explanation for declining. 719 Between pregnancy biologic variability of nuchal translucency Robin B. Kalish 1 , David Krantz 2 , Kayla Williams 3 , Stephen T. Chasen 1 1 Weill Cornell Medical College, Obstetrics and Gynecology, New York, NY, 2 PerkinElmer, NTD Laboratories, Melville, NY, 3 Weill Cornell Medical Center, Obstetrics and Gynecology, New York, NY OBJECTIVE: First trimester fetal nuchal translucency (NT) measure- ment is used as a screening test to assess risk for Down Syndrome. While chromosomal and structural abnormalities are associated with abnormal NT, the degree of biologic variation in the absence of any abnormalities is unclear. We sought to assess the correlation between NT in consecutive pregnancies. STUDY DESIGN: Women who had NT screening in our ultrasound unit in two consecutive pregnancies were included. Known cases of aneu- ploidy were excluded. NT data was converted to multiples of the me- dian (MoM) for pregnancies of the same gestational age. NT 95%ile for gestational age was considered abnormal. Spearman’s rho and Chi Square tests were used to correlate NT MoM and the likelihood of abnormal NT among the same women in subsequent pregnancies. Subgroup analysis was done according to ethnicity. RESULTS: 4147 women had NT screening in at least 2 consecutive pregnancies in our unit. 51 women with known aneuploidy in either pregnancy were excluded. Of the 4096 women included, there was a significant correlation between NT MoM in the 1st and 2nd preg- nancy (r.122, p.001). Women with an abnormal NT in the 1st pregnancy were significantly more likely to have an abnormal NT in the subsequent pregnancy (p.001). When stratifying the data ac- cording to ethnicity, a significant correlation between NT in consec- utive pregnancies was still present in White and Asian populations. CONCLUSION: There was a significant correlation for NT between con- secutive pregnancies in individual patients. Women having an abnor- mal NT in one euploid pregnancy, are more likely to have an abnor- mal NT in a subsequent pregnancy. This suggests that intrinsic factors contribute to NT measurements, and prior NT measurements could www.AJOG.org Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical-Disease Poster Session V Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology S319

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Page 1: 718: Why do women decline genetic amniocentesis?

STUDY DESIGN: 62 candidate genes for obligate twinning were identi-fied, including members of the Bone Morphogenetic Protein (BMP),Growth and Differentiation Factor (GDF), and IGF gene families andpathways. Marmoset specific nonsynonymous (meaning resulting inan amino acid change) substitutions (NS) were identified using the33-way eutherian mammal EPO alignments from Ensembl. These NSsubstitutions were compared, and only marmoset NS conservedamong all other haplorhines were retained. NS with a probable effecton protein function were identified using SIFT. In extensive valida-tions studies, exon amplicons of these NS were sequenced in 7 cal-litrichid and 3 non-callitrichid NWM species.RESULTS: 22 callitrichid-specific and validated NS were present in only14 genes (Table). Of interest, GDF9 and BMP15 variants have previ-ously been observed in sheep breeds which twin. The BMP15 NS is avaline to threonine conversion in the signal peptide. Two NS in GDF9occur in the propeptide, and include an asparagine to serine changethat disrupts glycosolyation.CONCLUSION: We have identified and validated callitrichid specific NSthat likely yield obligate twinning. Further characterization of theseNS will provide candidate regions for examination of human singlenucleotide polymorphisms that may have implications in twinning,and emphasize the discovery potential of primate comparativegenomics for human perinatal disorders.

718 Why do women decline genetic amniocentesis?Douglas Richards1, Lorna Rodriguez2,Melanie Adamsky3, Katherine Davidson3

1Intermountain Medical Center and the University of Utah,Maternal Fetal Medicine, Murray, UT, 2University of Florida,Maternal Fetal Medicine, Gainesville, FL, 3University ofFlorida, Obstetrics and Gynecology, Gainesville, FLOBJECTIVE: There has been a well-recognized decrease in the numberof women undergoing invasive genetic diagnosis. The purpose of thisstudy is to discover reasons that women decline testing.STUDY DESIGN: 3779 women having second trimester genetic counsel-ing between 10/2004 and 5/2010 at the University of Florida inGainesville were offered amniocentesis. Following the counseling ses-sion, patients intention to have amniocentesis was recorded by thegenetic counselor. After ultrasound evaluation, those who declinedthe procedure were asked to complete a simple questionnaire statingtheir reasons for refusal. Regression analysis was used to determineassociations between reasons for refusal and demographic factors, in-cluding age, parity, race/ethnicity, marital status and urban or ruralplace of residence.RESULTS: At the conclusion of the counseling session, 70% of patientshad decided whether they wanted amniocentesis. Of these, 75% de-clined. 30% patients were undecided, wanting to see if the ultrasoundwas OK before committing. Only 12% of these ultimately chose am-niocentesis. Of those who declined, for whom post-ultrasound ques-tionnaires were available, roughly two thirds chose worry about risks(risks), feeling reassured by non-invasive testing (reassured), and

abortion not being an option (no abortion) as reasons. 94% of declin-ers had more than one reason. No demographic factors were associ-ated with risks, or reassured. Ethnicity was strongly associated with noabortion as a reason (p�0.002); cited by 57 of 103 (45%) of blacks and59 of 110 (46%) of Hispanics, but only 340 of 534 (36%) of whites.Rural residency (p�0.004) and younger age (p�.02) were also asso-ciated with no abortion as a reason.CONCLUSION: Many patients use ultrasound findings to help them de-cide to have amniocentesis. Of undecided patients, the majority de-cline. Fear of complications, feeling reassured by non-invasive tests,and no abortion are cited roughly equally as reasons. Black or His-panic ethnicity, rural residence, and younger age are associated withno abortion as an explanation for declining.

719 Between pregnancy biologicvariability of nuchal translucencyRobin B. Kalish1, David Krantz2, KaylaWilliams3, Stephen T. Chasen1

1Weill Cornell Medical College, Obstetrics and Gynecology, New York,NY, 2PerkinElmer, NTD Laboratories, Melville, NY, 3Weill CornellMedical Center, Obstetrics and Gynecology, New York, NYOBJECTIVE: First trimester fetal nuchal translucency (NT) measure-ment is used as a screening test to assess risk for Down Syndrome.While chromosomal and structural abnormalities are associated withabnormal NT, the degree of biologic variation in the absence of anyabnormalities is unclear. We sought to assess the correlation betweenNT in consecutive pregnancies.STUDY DESIGN: Women who had NT screening in our ultrasound unitin two consecutive pregnancies were included. Known cases of aneu-ploidy were excluded. NT data was converted to multiples of the me-dian (MoM) for pregnancies of the same gestational age. NT �95%ilefor gestational age was considered abnormal. Spearman’s rho and ChiSquare tests were used to correlate NT MoM and the likelihood ofabnormal NT among the same women in subsequent pregnancies.Subgroup analysis was done according to ethnicity.RESULTS: 4147 women had NT screening in at least 2 consecutivepregnancies in our unit. 51 women with known aneuploidy in eitherpregnancy were excluded. Of the 4096 women included, there was asignificant correlation between NT MoM in the 1st and 2nd preg-nancy (r�.122, p�.001). Women with an abnormal NT in the 1stpregnancy were significantly more likely to have an abnormal NT inthe subsequent pregnancy (p�.001). When stratifying the data ac-cording to ethnicity, a significant correlation between NT in consec-utive pregnancies was still present in White and Asian populations.CONCLUSION: There was a significant correlation for NT between con-secutive pregnancies in individual patients. Women having an abnor-mal NT in one euploid pregnancy, are more likely to have an abnor-mal NT in a subsequent pregnancy. This suggests that intrinsic factorscontribute to NT measurements, and prior NT measurements could

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

Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology S319