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Triple marker (AFP, uE3,hCG) versus AFP plus free-beta in second trimester maternal serum screening for down syndrome: A prospective comparison study
390
S P O Abstracts
474 ~ m ~ x o v ' ~ e o x , ~
January 1995 Am J Obstet Gynecol
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V. Pa&91 ~, R. Nolan , N. iHu ' D. Packard ' E. ~ D e p t s . of OB/GYN and Anatomy , SUNY Health Science Center, Syracuse, NY; Pediatric Cardiology , Univ. of Rochester, Rochester, NY. OBJECTIVE: 5-Fluoro-2'-deoxyuridine (FdU) causes vascular injury in the limbs, skull and lumbosacral regions of chick embryos prior to the skeletal malformations. We studied the cardiovascular function in developing embryos following exposure to FdU. STUDY DESIGN: 0.026 ug FdU was injected with a 22 gauge needle in the yolk sac of Hamburger & Hamilton stage 18 white Leghorn chick embryos. We measured dorsal aortic blood pressure and flow simultaneously with a servonull system and 2 0 M H z pulsed-Doppler ultrasound at stages 21, 24 and 27 embryos. In addition to 34 experimental embryos, 12 uninjected and 21 saline injected eggs were used as normal and sham controls. Data was presented as mean ±SEM and analyzed by t-test. RESULTS~ Systolic pressure increased to 2.86f0.27 mm Hg (p<0.05) in the stage 27 FdU injected embryos when compared to normal (1.58±0.20 mm Hg) and sham control (2.02±0.22 mm Hg). Other parameters (diastolic pressure, blood flow, stroke volume) in experimental embryos were similar to the values of normal and sham controls in all stages. CONCLUSIONS: The teratogenic dose of FdU causes hypertension in experimental animals. Hematomas observed following exposure to FdU may result from vascular disruption caused by this hypertension.
475
P R E G N A N C Y C O M P L I C A T I O N S AND A D V E R S E P E T A L OUTCOME IN PATIENTS WITH DOUBLE POSITIVE SERUM S C R E E N I N G R E S U L T S . ~ J.A. CaniekX, L. Correiax, S.L Brewaterx, J.V, DalleyX, and M.A. Pagnotto x. Brown University/Women & Infants Hospital, Providence, RL O B J E C T I V E : To determine the rate of complications and adverse fetal outcome in patients who were screen positive for both open fetal defects and Down syndrome (double positive) alex triple m ~ k e r screeoing. STUDY DESIGN: All patients screened at our institution between 9/89 and 2194 and found to be double positive were identified. Each had an MSAb'P level of >2.0 MoM and a second trimester risk of Down syndrome (DS) of >1 in 270. Medical records were reviewed and the data tabulated. R E S U L T S : Among 42,407 patients screened, 75 had double positive results (1 in 565). Complete ascertainment was obtained in 70/75 (93%). Median age was 29 years (g6% under age 35). Median values of the triple markers were: AFP, 2.47 MoM; uE3, 0.63 MoM; hCG, 4.61 MoM. Median DS risk was I in 98. There were 3 twin gestations. Karyotypes were done in 52/70, with 2 abnormalities detected (1 DS and 1 inherited, apparently balanced translocation). Pregnancy complications or adverse outcome occurred in 44/70 (63%) eases. 16/70 (23%) resulted in nonviable offspring (11 IUFD, I with DS; 1 miscarriage; 3 neonatal losses, 1 with the balanced translocetion; 1 infant death after delivery at 28 wks). Complications associated with placental insufficiency were common, including hypertensive disorders in 22/70 (31%; CHTN in 6, PHI in 7, preeelampsia in 8, HELLP syndrome in 3), IUGR in 13/70 (18%), and bleeding or abruptiun in 10/70 (14%). Additiunal complications included preterm delivery in 19/70 (27%), preterm labor in 8/70 (11%), PROM in 2/70 (3%), GDM in 4/70 (6%), and chorioamnionitis in 2/70 (3%). The remaining 26/70 (37%) patients had uneventful pregnancies with term deliverT of AGA infants. C O N C L U S I O N S : Almost two-thirds of patients with double positive triple screening results had at least one significant corfiplication or adverse outcome. This study confwms and extends previously published smaLl data sets and demonstrates that a double positive screening result, while a rare event, must be considered a significant high-risk indicator.
476 TRIPLE MARKER (AFP,uE3,hCG) VERSUS AFP PLUS FREE-BETA IN
SECOND TRIMESTER MATERNAL SERUM SCREENING FOR DOWN SYNDROME: A PROSPECTIVE COMPARISON STUDY. L.H. Kellner k,x, Z. WeinerTM, R.R. Weiss2, M. Neuer L'~, G. Marlin' L M. Mueenuddint't, A. Bombard3, Dept. of Pathology t and Ob/Gyn2'3, WinthropUniversity Hospital ~, Mineola, and Albert Einstein College of Medicine 3, N.Y. OBJECTIVE: To compare triple marker screening with the combination of freebeta plus alpha-fetoprotein (AFP) in second trimester maternal serum screening for Down syndrome. STUDY DESIGN: Free-beta was concurrently assayed in 2349 maternal serum samples from non-black, pregnant women who were prospectively screened for Down syndrome with triple marker (AFP, uE3, and hCG) between 15-22 weeks gestation. Trivariate and bivariate Gaussian algorithms were used to calculate the risk for Down syndrome using the triple marker and AFP plus free-beta, respectively. Amniocentesis was offered when the second trimester risk tbr Down syndrome was > 1:270 using the triple marker. Gestational age was calculated from the last menstrual period unless ultrasonographic data was available. In addition, free-beta was retrospectively assayed in 12 cases of Down syndrome previously screened prospectively with the triple marker. RESULTS: Mean maternal age of our study was 29.8 (14-51) years. The mean of the Iog,o MoM+SD for hCG in unaffected and affected cases were - 0.004 +0.253 (p =0.0001 ) and 0.287-t-0.259 in contrast for free-beta 0.007+0.280 and 0.350-t-0.378 (p= 00001) respectively.The false positive rate using the triple marker was 8.0% compared with 12.8% using the free-beta plus AFP marker. All three cases of Down syndrome ascertained in our study were detected by the triple marker. One of 3 was detected with the AFP plus free-beta. Of the 12 additional cases of Down syndrome, 9 (75%) were screen positive with triple marker and 8 (67 %) were screen positive with the free-beta plus AFP. CONCLUSION: Detection rates overall were not significantly different, 12/15 for triple marker and 9/15 for AFP plus free-beta. However, the initial positive rate of second trimester maternal serum screening for Down syndrome is considerably higher using AFP plus free-beta compared with triple markers at a fixed risk cutoff. Our data do not support the claims of other studies that suggest AFP plus free-beta is superior to triple markers.
477 PREGNANCY O U T C O M E IN PATIENTS W I T H INCREASED RISK
FOR BOTH NEURAL TUBE DEFECTS AND DOWN SYNDROME DN Sailer. Jr.. CA French x, CJ Peterson x, RA Mooney x, DA Aryanx University of Rochester, Strong Memorial Hospital, Rochester, NY OBJECTIVE: To evaluate the outcome of pregnancies at increased risk for both neural tube defects (NTD) and Down syndrome (DS). STUDY DESIGN: Pregnancies undergoing maternal serum screening with AFP & hCG (14-25 wks) were reviewed. Between July 1991 & April 1994, pregnancies at increased risk for both NTD (AFP ~__2,0MoM) and DS (third trimester risk >1/307) were identified. Outcome data were obtained through a review of ultrasound, genetic and medical records. Multiple gestations (n=5) were excluded from further review. RESULTS: Of 19,645 pregnancies screened, 26 were confirmed as being at increased risk for both NTD and DS (1 per 756 screened pregnancies).The median maternal age was 30.5yrs. The median AFP was 2.34 MoM and the median hCG was 4.75 MoM. The median DS risk was 1 in 176. Outcomes: Anomalv/Comnfication Number Outcome None 12 8 SVD's, 4 C/S (Term Uncomplicated Delivery) (6 male, 6 female) 47,XXX 1 SVD at term 69,XXX 1 Termination Fetal Demise 4 (16-22wks) Polycystic Kidney Disease 1 Termination Gastroschisis 1 Neonatal Death Early PROM (- 15w) 1 Terraination Late PROM (Third Trimester) 3 34w C/S,2 SVDs @ 36w Type I Diabetes &Renal Failure 1 C/S at term Placenta Previa 1 C/S at 34 w Overall, two cases (7.7%) were aneuploid, four (15.4%) ended in fetal demise, three (11.5%) had pregnancy terminations and one (3.8%) resulted in neonatal death . Both aneupioid pregnancies developed preecclampsia. In a total of 8 cases (30.8%), there was a pregnancy loss or perinatal death. CONCLUSIONS: These data suggest that pregnancies at increased risk for both neural tube defects and Down syndrome are rare and are at markedly increased risk for anomalies and adverse pregnancy outcome.
S P O Abstracts
474 ~ m ~ x o v ' ~ e o x , ~
January 1995 Am J Obstet Gynecol
xmsc'r x o s
xN
eHxca~
mmR~OS
V. Pa&91 ~, R. Nolan , N. iHu ' D. Packard ' E. ~ D e p t s . of OB/GYN and Anatomy , SUNY Health Science Center, Syracuse, NY; Pediatric Cardiology , Univ. of Rochester, Rochester, NY. OBJECTIVE: 5-Fluoro-2'-deoxyuridine (FdU) causes vascular injury in the limbs, skull and lumbosacral regions of chick embryos prior to the skeletal malformations. We studied the cardiovascular function in developing embryos following exposure to FdU. STUDY DESIGN: 0.026 ug FdU was injected with a 22 gauge needle in the yolk sac of Hamburger & Hamilton stage 18 white Leghorn chick embryos. We measured dorsal aortic blood pressure and flow simultaneously with a servonull system and 2 0 M H z pulsed-Doppler ultrasound at stages 21, 24 and 27 embryos. In addition to 34 experimental embryos, 12 uninjected and 21 saline injected eggs were used as normal and sham controls. Data was presented as mean ±SEM and analyzed by t-test. RESULTS~ Systolic pressure increased to 2.86f0.27 mm Hg (p<0.05) in the stage 27 FdU injected embryos when compared to normal (1.58±0.20 mm Hg) and sham control (2.02±0.22 mm Hg). Other parameters (diastolic pressure, blood flow, stroke volume) in experimental embryos were similar to the values of normal and sham controls in all stages. CONCLUSIONS: The teratogenic dose of FdU causes hypertension in experimental animals. Hematomas observed following exposure to FdU may result from vascular disruption caused by this hypertension.
475
P R E G N A N C Y C O M P L I C A T I O N S AND A D V E R S E P E T A L OUTCOME IN PATIENTS WITH DOUBLE POSITIVE SERUM S C R E E N I N G R E S U L T S . ~ J.A. CaniekX, L. Correiax, S.L Brewaterx, J.V, DalleyX, and M.A. Pagnotto x. Brown University/Women & Infants Hospital, Providence, RL O B J E C T I V E : To determine the rate of complications and adverse fetal outcome in patients who were screen positive for both open fetal defects and Down syndrome (double positive) alex triple m ~ k e r screeoing. STUDY DESIGN: All patients screened at our institution between 9/89 and 2194 and found to be double positive were identified. Each had an MSAb'P level of >2.0 MoM and a second trimester risk of Down syndrome (DS) of >1 in 270. Medical records were reviewed and the data tabulated. R E S U L T S : Among 42,407 patients screened, 75 had double positive results (1 in 565). Complete ascertainment was obtained in 70/75 (93%). Median age was 29 years (g6% under age 35). Median values of the triple markers were: AFP, 2.47 MoM; uE3, 0.63 MoM; hCG, 4.61 MoM. Median DS risk was I in 98. There were 3 twin gestations. Karyotypes were done in 52/70, with 2 abnormalities detected (1 DS and 1 inherited, apparently balanced translocation). Pregnancy complications or adverse outcome occurred in 44/70 (63%) eases. 16/70 (23%) resulted in nonviable offspring (11 IUFD, I with DS; 1 miscarriage; 3 neonatal losses, 1 with the balanced translocetion; 1 infant death after delivery at 28 wks). Complications associated with placental insufficiency were common, including hypertensive disorders in 22/70 (31%; CHTN in 6, PHI in 7, preeelampsia in 8, HELLP syndrome in 3), IUGR in 13/70 (18%), and bleeding or abruptiun in 10/70 (14%). Additiunal complications included preterm delivery in 19/70 (27%), preterm labor in 8/70 (11%), PROM in 2/70 (3%), GDM in 4/70 (6%), and chorioamnionitis in 2/70 (3%). The remaining 26/70 (37%) patients had uneventful pregnancies with term deliverT of AGA infants. C O N C L U S I O N S : Almost two-thirds of patients with double positive triple screening results had at least one significant corfiplication or adverse outcome. This study confwms and extends previously published smaLl data sets and demonstrates that a double positive screening result, while a rare event, must be considered a significant high-risk indicator.
476 TRIPLE MARKER (AFP,uE3,hCG) VERSUS AFP PLUS FREE-BETA IN
SECOND TRIMESTER MATERNAL SERUM SCREENING FOR DOWN SYNDROME: A PROSPECTIVE COMPARISON STUDY. L.H. Kellner k,x, Z. WeinerTM, R.R. Weiss2, M. Neuer L'~, G. Marlin' L M. Mueenuddint't, A. Bombard3, Dept. of Pathology t and Ob/Gyn2'3, WinthropUniversity Hospital ~, Mineola, and Albert Einstein College of Medicine 3, N.Y. OBJECTIVE: To compare triple marker screening with the combination of freebeta plus alpha-fetoprotein (AFP) in second trimester maternal serum screening for Down syndrome. STUDY DESIGN: Free-beta was concurrently assayed in 2349 maternal serum samples from non-black, pregnant women who were prospectively screened for Down syndrome with triple marker (AFP, uE3, and hCG) between 15-22 weeks gestation. Trivariate and bivariate Gaussian algorithms were used to calculate the risk for Down syndrome using the triple marker and AFP plus free-beta, respectively. Amniocentesis was offered when the second trimester risk tbr Down syndrome was > 1:270 using the triple marker. Gestational age was calculated from the last menstrual period unless ultrasonographic data was available. In addition, free-beta was retrospectively assayed in 12 cases of Down syndrome previously screened prospectively with the triple marker. RESULTS: Mean maternal age of our study was 29.8 (14-51) years. The mean of the Iog,o MoM+SD for hCG in unaffected and affected cases were - 0.004 +0.253 (p =0.0001 ) and 0.287-t-0.259 in contrast for free-beta 0.007+0.280 and 0.350-t-0.378 (p= 00001) respectively.The false positive rate using the triple marker was 8.0% compared with 12.8% using the free-beta plus AFP marker. All three cases of Down syndrome ascertained in our study were detected by the triple marker. One of 3 was detected with the AFP plus free-beta. Of the 12 additional cases of Down syndrome, 9 (75%) were screen positive with triple marker and 8 (67 %) were screen positive with the free-beta plus AFP. CONCLUSION: Detection rates overall were not significantly different, 12/15 for triple marker and 9/15 for AFP plus free-beta. However, the initial positive rate of second trimester maternal serum screening for Down syndrome is considerably higher using AFP plus free-beta compared with triple markers at a fixed risk cutoff. Our data do not support the claims of other studies that suggest AFP plus free-beta is superior to triple markers.
477 PREGNANCY O U T C O M E IN PATIENTS W I T H INCREASED RISK
FOR BOTH NEURAL TUBE DEFECTS AND DOWN SYNDROME DN Sailer. Jr.. CA French x, CJ Peterson x, RA Mooney x, DA Aryanx University of Rochester, Strong Memorial Hospital, Rochester, NY OBJECTIVE: To evaluate the outcome of pregnancies at increased risk for both neural tube defects (NTD) and Down syndrome (DS). STUDY DESIGN: Pregnancies undergoing maternal serum screening with AFP & hCG (14-25 wks) were reviewed. Between July 1991 & April 1994, pregnancies at increased risk for both NTD (AFP ~__2,0MoM) and DS (third trimester risk >1/307) were identified. Outcome data were obtained through a review of ultrasound, genetic and medical records. Multiple gestations (n=5) were excluded from further review. RESULTS: Of 19,645 pregnancies screened, 26 were confirmed as being at increased risk for both NTD and DS (1 per 756 screened pregnancies).The median maternal age was 30.5yrs. The median AFP was 2.34 MoM and the median hCG was 4.75 MoM. The median DS risk was 1 in 176. Outcomes: Anomalv/Comnfication Number Outcome None 12 8 SVD's, 4 C/S (Term Uncomplicated Delivery) (6 male, 6 female) 47,XXX 1 SVD at term 69,XXX 1 Termination Fetal Demise 4 (16-22wks) Polycystic Kidney Disease 1 Termination Gastroschisis 1 Neonatal Death Early PROM (- 15w) 1 Terraination Late PROM (Third Trimester) 3 34w C/S,2 SVDs @ 36w Type I Diabetes &Renal Failure 1 C/S at term Placenta Previa 1 C/S at 34 w Overall, two cases (7.7%) were aneuploid, four (15.4%) ended in fetal demise, three (11.5%) had pregnancy terminations and one (3.8%) resulted in neonatal death . Both aneupioid pregnancies developed preecclampsia. In a total of 8 cases (30.8%), there was a pregnancy loss or perinatal death. CONCLUSIONS: These data suggest that pregnancies at increased risk for both neural tube defects and Down syndrome are rare and are at markedly increased risk for anomalies and adverse pregnancy outcome.