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263 Free Beta HCG in Down Syndrome Screening
350
260
SPO Abstracts
January 1992 Am J Obstet Gyneco1
SIGNfiCANCE OF AIooNOllC FWD PLATELET FACTOR 4 AND BETA-lHROMBOGLOBUUNIN GENEllCMNOCENTESIS. AA Saleh NB Isada, MP Johnson, MI Evans, T Ozawa, MP Dombrowski, M Treadwell, EF Mammen, Dept Ob/Gyn, and Center for Fetal Diagnosis and Therapy, Hutzel HospitalWayne State University, Detro~, MI. Platelet factor 4 (PF4) and betathromboglobulin (BTG), unique markers of irreversible platelet activation, have not been evaluated in amniotic fluid. While PF4 is mainly cleared by endothelium and to a lesser extent by kidneys, BTG is only cleared by kidneys. Therefore, amniotic fluid PF4 and BTG levels may reflect fetal platelet activation, endothelial and/or renal function. We measured PF4 and BTG by ELISA in amniotic fluid from 78 patients w~h normal a·fetoprotein (AFP) and 24 with high AFP (anencephaly 5, gastroschisis 5, fetal demise 8, cystic hygroma 1, placental hematoma 1, hydrocephalus 4). All pregnancies ranged from 15-20 weeks gestation. Results are shown below (mean ± SO). Mann· Whitney U test was used. AfP: Gestciion~8)
Nanna! (n-78)
17.5.t..1.7
Abnormal (n-24)
18± 1.7
Signilicance
N.S.
PF4(llJImI)
1.3;12.3
4.6.t. 10
pcO.OO1
BTG(IIJIrrl)
18.2.t13.8
3Ot,26.5
peO.O()1
PF4 and BTG correlated significantly with AFP (expressed as MOM) only in the abnormal group (p<0.05, p
261
PREQOERCY OF CONFIBED PLACENTAL MOSAICISM IN PREGNANCIES WITH INTRAUTERINE GROWTH RETARDATION. k. Wilkins-Haug, ~.F. Greene,
D.J. Roberts , C.C. Morton , Depts of Ob/Gyn and Pathology, Brigham and Women's Hospital, Harvard Medical School Confined placental mosaicism (CPM) occurs in conjunction with a karyotYl?ically normal fetus i l l 2-3% of chorionl.c Vl.llus samples. An increased rate of intrauterine growth retardation (IUGR) has been reported in these pregnancies. Among third trimester pregnancies complicated by IUGR, however, the frequency and clinical characteristics of CPM are unknown. We report karyotype analyses of amnion, chorion, villi and cord blood from 12 pregnancies with IUGR (birth weight <10%). In two cases, mosaicism was detected in all placental lines: 46,XX/48,XX,+17,+21 (55%/45%) and 46,XX/92,XXXX (66%/34%). The aneuploid line was confirmed in uncultured amnion preparations utilizing fluorescent in situ hybridization with an alpha satellite probe specific to chromosome 17. In a third case, a 46,XX/92,XXXX (75%/25%) mosaicism was confined to the amnion. In all cases, cord blood karyotypes were normal. Comparison of the ultrasound findings, perinatal complications and placental pathology from these cases provides a preliminary clinical description of the IUGR fetus with placental mosaicism. We conclude that CPM occurs with greater frequency among pregnancies with IUGR. Attempts to identify additional cases and to delineate further the associated clinical characteristics are ongoing.
262 THE EFFECTS OF ETHANOL ON LINOLEIC ACID INCORPORATION AND METABOLISM BY HUMAN PLACENTAL TISSUE I~ VITRO. E. Kirk,X P. Ogburn, R. Holman,x J. Miles,x Dept. OB/GYN & Internal Medicine, Mayo Clinic & Hormel Institute, Rochester &Austin, MN The teratogenic effects of ethanol (ETOH) may involve alterations in essential fatty acid metabolism. To study this, [1_14C] linoleic acid (LA) was added to human placental tissue in DMEM media (n=7) exposed to 95% oxygen at 37 0 in a shaking incubator with varying concentrations of alcohol from 0-200 mg/dL. Samples of tissue and media were removed and analyzed at intervals over 24 hrs. We found significant uptake of LA into placental tissue (47.8% + 4.8% p<.Ol) at 12 hrs. ETOH did not significantly affect this uptake. After 12 hrs. inCUbation the conversion of LA to intermediate fatty acids leading to arachidonic acid decreased by more than 40% at even the lowest ETOH concentrations. This decrease was significant (p<.05) at ETOH concentrations of 100 & 200 mg/dL. Our work supports evidence of deranged LA metabolism secondary to ETOH in placental tissue in vitro.
263
FREE BETA HCG IN DOWN SYNDROME SCREENING. L Larsen, K. Garver,x S. Frank,x J. Macri,x Dept. OB/GYN, George Washington Univ. Med. Clr., Washington, D.C., Dept. Medical Genetics, Western Pennsylvania Hosp., Pittsburgh, PA, NTD Laboratories, Inc., Carle Place, NY. Recent reports have demonstrated enhanced detection efficiency in Down syndrome screening using Free Beta hCG, especially in early weeks of gestation « 17 weeks). We have coUaborated in a blind study usin~ samples coUected at a single center and maintained at -20 C. AFP and Free Beta were measured in a single laboratory utilizing in-house ELISA technology. Patient -specific risks were calculated using linear multivariate discriminant analysis. The normative data set for both MSAFP and Free Beta was established on 2,900 pregnancy samples, all of which were: under 35 years of age, between gestational weeks 14-22, non-diabetic, singleton, white pregnancies. The blind study set consisted of 50 patient samples, 42 of which were normal outcomes and 8 conflfmed cases of trisomy 21. The blind study set consisted of 12 patients at or above 35 and 38 patients under 35 years of age. Nine cases feU below 17 weeks of gestation and 41 at or above. Of the 8 cases of Down syndrome, 6 (75%) demonstrated significantly increased risk and were thus correctly identified. In 4 cases where pregnancy outcome was normal, biochemical results indicated an increased risk for Down syndrome. In 3 of these cases, maternal age was greater than 35. We conclude that this is further confirmation of the usefulness of Free Beta heG as a marker in Down syndrome screening.
260
SPO Abstracts
January 1992 Am J Obstet Gyneco1
SIGNfiCANCE OF AIooNOllC FWD PLATELET FACTOR 4 AND BETA-lHROMBOGLOBUUNIN GENEllCMNOCENTESIS. AA Saleh NB Isada, MP Johnson, MI Evans, T Ozawa, MP Dombrowski, M Treadwell, EF Mammen, Dept Ob/Gyn, and Center for Fetal Diagnosis and Therapy, Hutzel HospitalWayne State University, Detro~, MI. Platelet factor 4 (PF4) and betathromboglobulin (BTG), unique markers of irreversible platelet activation, have not been evaluated in amniotic fluid. While PF4 is mainly cleared by endothelium and to a lesser extent by kidneys, BTG is only cleared by kidneys. Therefore, amniotic fluid PF4 and BTG levels may reflect fetal platelet activation, endothelial and/or renal function. We measured PF4 and BTG by ELISA in amniotic fluid from 78 patients w~h normal a·fetoprotein (AFP) and 24 with high AFP (anencephaly 5, gastroschisis 5, fetal demise 8, cystic hygroma 1, placental hematoma 1, hydrocephalus 4). All pregnancies ranged from 15-20 weeks gestation. Results are shown below (mean ± SO). Mann· Whitney U test was used. AfP: Gestciion~8)
Nanna! (n-78)
17.5.t..1.7
Abnormal (n-24)
18± 1.7
Signilicance
N.S.
PF4(llJImI)
1.3;12.3
4.6.t. 10
pcO.OO1
BTG(IIJIrrl)
18.2.t13.8
3Ot,26.5
peO.O()1
PF4 and BTG correlated significantly with AFP (expressed as MOM) only in the abnormal group (p<0.05, p
261
PREQOERCY OF CONFIBED PLACENTAL MOSAICISM IN PREGNANCIES WITH INTRAUTERINE GROWTH RETARDATION. k. Wilkins-Haug, ~.F. Greene,
D.J. Roberts , C.C. Morton , Depts of Ob/Gyn and Pathology, Brigham and Women's Hospital, Harvard Medical School Confined placental mosaicism (CPM) occurs in conjunction with a karyotYl?ically normal fetus i l l 2-3% of chorionl.c Vl.llus samples. An increased rate of intrauterine growth retardation (IUGR) has been reported in these pregnancies. Among third trimester pregnancies complicated by IUGR, however, the frequency and clinical characteristics of CPM are unknown. We report karyotype analyses of amnion, chorion, villi and cord blood from 12 pregnancies with IUGR (birth weight <10%). In two cases, mosaicism was detected in all placental lines: 46,XX/48,XX,+17,+21 (55%/45%) and 46,XX/92,XXXX (66%/34%). The aneuploid line was confirmed in uncultured amnion preparations utilizing fluorescent in situ hybridization with an alpha satellite probe specific to chromosome 17. In a third case, a 46,XX/92,XXXX (75%/25%) mosaicism was confined to the amnion. In all cases, cord blood karyotypes were normal. Comparison of the ultrasound findings, perinatal complications and placental pathology from these cases provides a preliminary clinical description of the IUGR fetus with placental mosaicism. We conclude that CPM occurs with greater frequency among pregnancies with IUGR. Attempts to identify additional cases and to delineate further the associated clinical characteristics are ongoing.
262 THE EFFECTS OF ETHANOL ON LINOLEIC ACID INCORPORATION AND METABOLISM BY HUMAN PLACENTAL TISSUE I~ VITRO. E. Kirk,X P. Ogburn, R. Holman,x J. Miles,x Dept. OB/GYN & Internal Medicine, Mayo Clinic & Hormel Institute, Rochester &Austin, MN The teratogenic effects of ethanol (ETOH) may involve alterations in essential fatty acid metabolism. To study this, [1_14C] linoleic acid (LA) was added to human placental tissue in DMEM media (n=7) exposed to 95% oxygen at 37 0 in a shaking incubator with varying concentrations of alcohol from 0-200 mg/dL. Samples of tissue and media were removed and analyzed at intervals over 24 hrs. We found significant uptake of LA into placental tissue (47.8% + 4.8% p<.Ol) at 12 hrs. ETOH did not significantly affect this uptake. After 12 hrs. inCUbation the conversion of LA to intermediate fatty acids leading to arachidonic acid decreased by more than 40% at even the lowest ETOH concentrations. This decrease was significant (p<.05) at ETOH concentrations of 100 & 200 mg/dL. Our work supports evidence of deranged LA metabolism secondary to ETOH in placental tissue in vitro.
263
FREE BETA HCG IN DOWN SYNDROME SCREENING. L Larsen, K. Garver,x S. Frank,x J. Macri,x Dept. OB/GYN, George Washington Univ. Med. Clr., Washington, D.C., Dept. Medical Genetics, Western Pennsylvania Hosp., Pittsburgh, PA, NTD Laboratories, Inc., Carle Place, NY. Recent reports have demonstrated enhanced detection efficiency in Down syndrome screening using Free Beta hCG, especially in early weeks of gestation « 17 weeks). We have coUaborated in a blind study usin~ samples coUected at a single center and maintained at -20 C. AFP and Free Beta were measured in a single laboratory utilizing in-house ELISA technology. Patient -specific risks were calculated using linear multivariate discriminant analysis. The normative data set for both MSAFP and Free Beta was established on 2,900 pregnancy samples, all of which were: under 35 years of age, between gestational weeks 14-22, non-diabetic, singleton, white pregnancies. The blind study set consisted of 50 patient samples, 42 of which were normal outcomes and 8 conflfmed cases of trisomy 21. The blind study set consisted of 12 patients at or above 35 and 38 patients under 35 years of age. Nine cases feU below 17 weeks of gestation and 41 at or above. Of the 8 cases of Down syndrome, 6 (75%) demonstrated significantly increased risk and were thus correctly identified. In 4 cases where pregnancy outcome was normal, biochemical results indicated an increased risk for Down syndrome. In 3 of these cases, maternal age was greater than 35. We conclude that this is further confirmation of the usefulness of Free Beta heG as a marker in Down syndrome screening.