- Email: [email protected]
216: Detection of chromosome abnormalities by sequential screening with first and second trimester serum and nuchal translucency
Poster Session I
ajog.org CONCLUSION: Late entrance to prenatal care is appears to be independently associated with neonatal and infant death.
abnormality, fetal demise, prematurity, and structurally abnormal fetus.
216 Detection of chromosome abnormalities by sequential screening with first and second trimester serum and nuchal translucency
215 Outcomes of pregnancies with more than one positive prenatal screening result 1
1
2
1
Rebecca Baer , Robert Currier , Mary Norton , Monica Flessel , Sara Goldman1, Dena Towner3, Laura Jelliffe-Pawlowski1 1
California Department of Public Health, Genetic Disease Screening Program, Richmond, CA, 2University of California School of Medicine, San Francisco, Department of Obstetrics, Gynecology and Reproductive Sciences, San Francisco, CA, 3University of Hawaii, Division of Maternal Fetal Medicine, Honolulu, HI
OBJECTIVE: To describe adverse outcomes and fetal abnormalities
among women with a positive prenatal screening result for more than one disorder. STUDY DESIGN: Study participants were drawn from a population of 452,901 women pregnant with singletons entering the California Prenatal Screening Program in their first-trimester. Risk assessment was provided for trisomy 21 (T21) and trisomy 18 (T18) in the firsttrimester and T21, T18, neural tube defects (NTD), and SmithLemli-Opitz syndrome (SLOS) in the second-trimester. Inclusion in this study required positive screening for more than one of the screened conditions (e.g. screen-positive for T21 and neural tube defect) and completed outcome of pregnancy survey. RESULTS: 314 women who screened positive for more than one disorder and had a completed outcome of pregnancy survey were identified. Nearly 37% of these pregnancies had a fetus with a chromosomal abnormality (15.3% T21, 13.4% T18, 3.8% T13 and 4.5% other chromosomal abnormalities). Of the chromosomally normal pregnancies, 7.1% had a fetus with a major structural birth defect. Of the pregnancies without a fetus with a chromosomal abnormality or major structural birth defect, 23.4% ended in fetal demise, 19.0% ended in preterm birth. Overall, only 22.0% of these pregnancies had a term infant of an appropriate weight for gestational age. CONCLUSION: Although it is rare to screen positive for more than one condition, such results indicate great risk for chromosomal
Rebecca Baer1, Monica Flessel1, Laura Jelliffe-Pawlowski1, Sara Goldman1, Louanne Hudgins2, Andrew Hull3, Mary Norton4, Robert Currier1
1 California Department of Public Health, Genetic Disease Screening Program, Richmond, CA, 2Stanford University, Division of Medical Genetics, Stanford, CA, 3University of California San Diego, Center for Maternal-Fetal Care & Genetics, San Diego, CA, 4University of California, San Francisco, Department of Obstetrics, Gynecology and Reproductive Sciences, San Francisco, CA
OBJECTIVE: To determine the detection rate (DR) of the California
Prenatal Screening (PNS) Program for chromosomal abnormalities using sequential screening with first and second trimester serum and nuchal translucency (NT). STUDY DESIGN: The study cohort included all singleton pregnancies with estimated delivery dates from August 2009 to December 2012 who had 1st and 2nd trimester sequential screening through the California PNS Program. Women with screen positive results are offered referral to a State-approved Prenatal Diagnostic Center (PDC) for genetic counseling and diagnostic services. Results from PDC visits are submitted to the Program electronically. State regulations require reporting of all chromosome abnormalities diagnosed in a fetus or infant <1 year of age; these results were also collected. DR and false positive rates (FPR) were calculated for chromosome abnormalities. RESULTS: 452,901 pregnant women were screened, 16,101 were screen positive for Down syndrome (DS) only; 425 were screen positive for T18; 1105 had an NT >3.5 mm; and 3536 were screen positive for neural tube defects, Smith-Lemli-Opitz syndrome, or for multiple conditions. A total of 2575 chromosomal abnormalities were identified in the cohort, including 1276 DS; 323 T18; 123 T13; 161 45,X; 67 triploidy and 625 other abnormalities. The DRs were: DS, 92.9%; T18, 93.5%; T13, 81.3%; 45,X, 80.1% and triploidy, 91.0%. The DR for other, less common chromosome abnormalities was 50%. The overall DR for all chromosome abnormalities was 81.6% at an overall false positive rate of 4.11%. CONCLUSION: The DR of sequential screening for DS, T18 and triploidy were >90%, and for T13 and 45,X were >80% at an overall program FPR of 4.11%. Although the program is designed to screen primarily for DS and T18, over 80% of all chromosomal abnormalities were detected. Sequential screening provides comprehensive screening for the broad range of karyotype abnormalities seen in the population.
Supplement to JANUARY 2015 American Journal of Obstetrics & Gynecology
S121
Poster Session I Program detection rates of major aneuploides and all other chromosome abnormalities among women with sequential screening
217 Amniocentesis and CVS skill as measured by reinsertion rates: is annual provider volume a factor?
Robert Currier1, Sara Goldman1, Amen Ness2, Manuel Porto3, Cheryl Ikeda1, Jamie Matteson1, Mary Norton4 1
California Dept. of Public Health, Genetic Disease Screening Program, Richmond, CA, 2Stanford University, Dept of Obstetrics and Gynecology, Palo Alto, CA, 3UC Irvine School of Medicine, Dept of Obstetrics and Gynecology, Irvine, CA, 4UCSF, Dept. of Obstetrics, Gynecology and Reproductive Sciences, San Francisco, CA
OBJECTIVE: To determine the annual volume of diagnostic procedures (amniocentesis and chorionic villus sampling (CVS)) below which the skill of the provider is detrimentally affected. STUDY DESIGN: Amniocentesis and CVS providers approved to practice at Prenatal Diagnosis Centers in California are required to submit semi-annual reports of a sequential set of procedures. Each reported case includes: number of fetuses, number of insertions, culture failure, fetal abnormality, and loss of a normal fetus by the time of reporting karyotype results. Results of these reports from 2010 to 2013 were analyzed, and the annual numbers of procedures performed and of cases with excess insertions were determined for each provider. “Excess insertions” was defined as more than one insertion per fetus. The percentage of providers having an elevated excess insertion rate was stratified according to provider annual volume. An elevated excess insertion rate was defined as excess insertions in >5% of amniocenteses or >10% of CVS procedures. The association of annual volume with elevated excess insertion rates was analyzed by logistic regression. RESULTS: 211 of 286 amniocentesis and 102 of 139 CVS providers submitted reports. The number of reports with excess insertions was lower for amniocentesis providers with an annual volume >60 (p<0.05 for 60 to 80 and p<0.0001 for >80) and for CVS providers with an annual volume >80 (p<0.0001). Providers performing >80 procedures per year submitted no reports of elevated excess insertions. At <40 procedures per year, approximately 14% of amniocentesis providers, and 23% of CVS providers reported an elevated excess insertion rate. 69% of amniocentesis providers and 78% of CVS providers report annual volumes of <40 procedures/ year. CONCLUSION: Maintaining an adequate volume of diagnostic procedures is important to maintain skill, as measured by the number of insertions. A significant proportion of prenatal diagnosis providers perform fewer procedures than necessary to maintain a high level of skill.
ajog.org Amniocentesis and chorionic villus sampling provider annual volume and excess insertion rates.
218 Standardized fetal growth curves according to world health organization recommendations (GAMLSS analysis) in a low-risk caucasian population
Sander Galjaard1, Roland Devlieger1, Lieveke Ameye2, Anne Pexsters1, Christoph Lees3, Tom Bourne2, Dirk Timmerman1
1 KU Leuven, University Hospitals, Belgium, Department of Development and Regeneration: Pregnancy, Fetus and Neonate, Gynaecology and Obstetrics, Leuven, Belgium, 2KU Leuven Department of Development and Regeneration, Leuven, Belgium, 3NHS Teaching Hospital, London, United Kingdom
OBJECTIVE: To develop fetal growth curves for a low risk population according to the latest WHO Multicentre Growth Reference Study Group recommendations. STUDY DESIGN: A retrospective longitudinal cohort study of firstsecond- and third trimester fetal ultrasound examinations was conducted in the period 2002-2012 in an academic teaching hospital. The data was selected using the following criteria: routine examinations in uncomplicated singleton pregnancy, Caucasian ethnicity, gestational age confirmed by a crown rump length (CRL) measurement (3-83mm) in the first trimester and exclusion if more than 3 ultrasound scans per pregnancy were performed. Examinations were only considered if containing complete data of all four fetal routine fetal measurements -BiParietal Diameter (BPD), Head Circumference (HC), Abdominal Circumference (AC) and Femur Length (FL). GAMLSS (Generalized Additive Model Location, Scale and Shape) was used to align the timeframes of measurements and create longitudinal growth curves for the four fetal measurements. Birth measurements were linked. RESULTS: A total of 89.933 scans were selected from the AstraiaÓ ultrasound database. After restriction, a total of 27.680 scans remained representing 12.368 pregnancies. Construction of fetal growth curves for BPD, HC, AC and FL for the gestational age 12 to 40 weeks, for boys, girls and the total group was performed. The HC and BPD were significant larger in boys compared to girls from 20 weeks onwards. Birth measurement confirmed this difference. CONCLUSION: Novel longitudinal ante-natal growth curves in a lowrisk population were constructed in accordance to the latest recommendations on ultrasound quality and growth statistics.
S122 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2015
ajog.org CONCLUSION: Late entrance to prenatal care is appears to be independently associated with neonatal and infant death.
abnormality, fetal demise, prematurity, and structurally abnormal fetus.
216 Detection of chromosome abnormalities by sequential screening with first and second trimester serum and nuchal translucency
215 Outcomes of pregnancies with more than one positive prenatal screening result 1
1
2
1
Rebecca Baer , Robert Currier , Mary Norton , Monica Flessel , Sara Goldman1, Dena Towner3, Laura Jelliffe-Pawlowski1 1
California Department of Public Health, Genetic Disease Screening Program, Richmond, CA, 2University of California School of Medicine, San Francisco, Department of Obstetrics, Gynecology and Reproductive Sciences, San Francisco, CA, 3University of Hawaii, Division of Maternal Fetal Medicine, Honolulu, HI
OBJECTIVE: To describe adverse outcomes and fetal abnormalities
among women with a positive prenatal screening result for more than one disorder. STUDY DESIGN: Study participants were drawn from a population of 452,901 women pregnant with singletons entering the California Prenatal Screening Program in their first-trimester. Risk assessment was provided for trisomy 21 (T21) and trisomy 18 (T18) in the firsttrimester and T21, T18, neural tube defects (NTD), and SmithLemli-Opitz syndrome (SLOS) in the second-trimester. Inclusion in this study required positive screening for more than one of the screened conditions (e.g. screen-positive for T21 and neural tube defect) and completed outcome of pregnancy survey. RESULTS: 314 women who screened positive for more than one disorder and had a completed outcome of pregnancy survey were identified. Nearly 37% of these pregnancies had a fetus with a chromosomal abnormality (15.3% T21, 13.4% T18, 3.8% T13 and 4.5% other chromosomal abnormalities). Of the chromosomally normal pregnancies, 7.1% had a fetus with a major structural birth defect. Of the pregnancies without a fetus with a chromosomal abnormality or major structural birth defect, 23.4% ended in fetal demise, 19.0% ended in preterm birth. Overall, only 22.0% of these pregnancies had a term infant of an appropriate weight for gestational age. CONCLUSION: Although it is rare to screen positive for more than one condition, such results indicate great risk for chromosomal
Rebecca Baer1, Monica Flessel1, Laura Jelliffe-Pawlowski1, Sara Goldman1, Louanne Hudgins2, Andrew Hull3, Mary Norton4, Robert Currier1
1 California Department of Public Health, Genetic Disease Screening Program, Richmond, CA, 2Stanford University, Division of Medical Genetics, Stanford, CA, 3University of California San Diego, Center for Maternal-Fetal Care & Genetics, San Diego, CA, 4University of California, San Francisco, Department of Obstetrics, Gynecology and Reproductive Sciences, San Francisco, CA
OBJECTIVE: To determine the detection rate (DR) of the California
Prenatal Screening (PNS) Program for chromosomal abnormalities using sequential screening with first and second trimester serum and nuchal translucency (NT). STUDY DESIGN: The study cohort included all singleton pregnancies with estimated delivery dates from August 2009 to December 2012 who had 1st and 2nd trimester sequential screening through the California PNS Program. Women with screen positive results are offered referral to a State-approved Prenatal Diagnostic Center (PDC) for genetic counseling and diagnostic services. Results from PDC visits are submitted to the Program electronically. State regulations require reporting of all chromosome abnormalities diagnosed in a fetus or infant <1 year of age; these results were also collected. DR and false positive rates (FPR) were calculated for chromosome abnormalities. RESULTS: 452,901 pregnant women were screened, 16,101 were screen positive for Down syndrome (DS) only; 425 were screen positive for T18; 1105 had an NT >3.5 mm; and 3536 were screen positive for neural tube defects, Smith-Lemli-Opitz syndrome, or for multiple conditions. A total of 2575 chromosomal abnormalities were identified in the cohort, including 1276 DS; 323 T18; 123 T13; 161 45,X; 67 triploidy and 625 other abnormalities. The DRs were: DS, 92.9%; T18, 93.5%; T13, 81.3%; 45,X, 80.1% and triploidy, 91.0%. The DR for other, less common chromosome abnormalities was 50%. The overall DR for all chromosome abnormalities was 81.6% at an overall false positive rate of 4.11%. CONCLUSION: The DR of sequential screening for DS, T18 and triploidy were >90%, and for T13 and 45,X were >80% at an overall program FPR of 4.11%. Although the program is designed to screen primarily for DS and T18, over 80% of all chromosomal abnormalities were detected. Sequential screening provides comprehensive screening for the broad range of karyotype abnormalities seen in the population.
Supplement to JANUARY 2015 American Journal of Obstetrics & Gynecology
S121
Poster Session I Program detection rates of major aneuploides and all other chromosome abnormalities among women with sequential screening
217 Amniocentesis and CVS skill as measured by reinsertion rates: is annual provider volume a factor?
Robert Currier1, Sara Goldman1, Amen Ness2, Manuel Porto3, Cheryl Ikeda1, Jamie Matteson1, Mary Norton4 1
California Dept. of Public Health, Genetic Disease Screening Program, Richmond, CA, 2Stanford University, Dept of Obstetrics and Gynecology, Palo Alto, CA, 3UC Irvine School of Medicine, Dept of Obstetrics and Gynecology, Irvine, CA, 4UCSF, Dept. of Obstetrics, Gynecology and Reproductive Sciences, San Francisco, CA
OBJECTIVE: To determine the annual volume of diagnostic procedures (amniocentesis and chorionic villus sampling (CVS)) below which the skill of the provider is detrimentally affected. STUDY DESIGN: Amniocentesis and CVS providers approved to practice at Prenatal Diagnosis Centers in California are required to submit semi-annual reports of a sequential set of procedures. Each reported case includes: number of fetuses, number of insertions, culture failure, fetal abnormality, and loss of a normal fetus by the time of reporting karyotype results. Results of these reports from 2010 to 2013 were analyzed, and the annual numbers of procedures performed and of cases with excess insertions were determined for each provider. “Excess insertions” was defined as more than one insertion per fetus. The percentage of providers having an elevated excess insertion rate was stratified according to provider annual volume. An elevated excess insertion rate was defined as excess insertions in >5% of amniocenteses or >10% of CVS procedures. The association of annual volume with elevated excess insertion rates was analyzed by logistic regression. RESULTS: 211 of 286 amniocentesis and 102 of 139 CVS providers submitted reports. The number of reports with excess insertions was lower for amniocentesis providers with an annual volume >60 (p<0.05 for 60 to 80 and p<0.0001 for >80) and for CVS providers with an annual volume >80 (p<0.0001). Providers performing >80 procedures per year submitted no reports of elevated excess insertions. At <40 procedures per year, approximately 14% of amniocentesis providers, and 23% of CVS providers reported an elevated excess insertion rate. 69% of amniocentesis providers and 78% of CVS providers report annual volumes of <40 procedures/ year. CONCLUSION: Maintaining an adequate volume of diagnostic procedures is important to maintain skill, as measured by the number of insertions. A significant proportion of prenatal diagnosis providers perform fewer procedures than necessary to maintain a high level of skill.
ajog.org Amniocentesis and chorionic villus sampling provider annual volume and excess insertion rates.
218 Standardized fetal growth curves according to world health organization recommendations (GAMLSS analysis) in a low-risk caucasian population
Sander Galjaard1, Roland Devlieger1, Lieveke Ameye2, Anne Pexsters1, Christoph Lees3, Tom Bourne2, Dirk Timmerman1
1 KU Leuven, University Hospitals, Belgium, Department of Development and Regeneration: Pregnancy, Fetus and Neonate, Gynaecology and Obstetrics, Leuven, Belgium, 2KU Leuven Department of Development and Regeneration, Leuven, Belgium, 3NHS Teaching Hospital, London, United Kingdom
OBJECTIVE: To develop fetal growth curves for a low risk population according to the latest WHO Multicentre Growth Reference Study Group recommendations. STUDY DESIGN: A retrospective longitudinal cohort study of firstsecond- and third trimester fetal ultrasound examinations was conducted in the period 2002-2012 in an academic teaching hospital. The data was selected using the following criteria: routine examinations in uncomplicated singleton pregnancy, Caucasian ethnicity, gestational age confirmed by a crown rump length (CRL) measurement (3-83mm) in the first trimester and exclusion if more than 3 ultrasound scans per pregnancy were performed. Examinations were only considered if containing complete data of all four fetal routine fetal measurements -BiParietal Diameter (BPD), Head Circumference (HC), Abdominal Circumference (AC) and Femur Length (FL). GAMLSS (Generalized Additive Model Location, Scale and Shape) was used to align the timeframes of measurements and create longitudinal growth curves for the four fetal measurements. Birth measurements were linked. RESULTS: A total of 89.933 scans were selected from the AstraiaÓ ultrasound database. After restriction, a total of 27.680 scans remained representing 12.368 pregnancies. Construction of fetal growth curves for BPD, HC, AC and FL for the gestational age 12 to 40 weeks, for boys, girls and the total group was performed. The HC and BPD were significant larger in boys compared to girls from 20 weeks onwards. Birth measurement confirmed this difference. CONCLUSION: Novel longitudinal ante-natal growth curves in a lowrisk population were constructed in accordance to the latest recommendations on ultrasound quality and growth statistics.
S122 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2015