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20 Mid-Trimester Echogenic Bowel and Chromosomal Abnormalities
SPO Abstracts
Volume 166 N umber I, Part 2
19 A PROSPECTIVE EVALUATION OF TRIPLE MARKER
MATERNAL SERUM SCREENING FOR TRISOMY-2l. EY cheng,X DA Luthy, DE Hickok, R Lieppman, RG Resta,X M Williams, x A Zebelman,x F Luthardt,X Swedish HOsp. Med. Ctr., Seattle WA Early data suggest the use of triple marker analysis from maternal serum may be an effective screening tool for the prenatal diagnosis of Trisomy-21. From 1/1/90 to 8/15/91 we evaluated the triple marker screen obtained at 16-18 weeks gestation in singleton, non-diabetic pregnancies, using MSAFP (HYBERTECH), unconjugated estriol, and total HCG (AMERSHAM) as the analytes measured. We defined a midtrimester risk for Trisomy-2l' of ~1:195 as a positive screen. Pilot studies indicated that 7% of pregnancies would be screen-positive and approximately 2/3 of all cases of Trisomy-21 could be detected. During the 20-month study period 7785 pregnancies were tested with a mean maternal age of 29.3±4.8. 572 pregnancies (7.5%) were screen-positive. 298 of the 7785 pregnancies screened (3.8%) eventually underwent amniocentesis, yielding 21 cases of Trisomy-21. Twenty-one of 298 of amniocenteses (PVP=7%) resulted in a diagnosis of Trisomy-21, comparing favorably to amniocenteses for advanced maternal age, in which 1-2% of procedures yield Trisomy-21. The use of 3 markers (MSAFP, HCG, estriol) improved screening performance, compared to MSAFP and HCG without estriol. The data suggest triple marker analysis is an effective prenatal screen for Trisomy-21.
20
MID-TRIMESTER ECHOGENIC BO~EL AND CHROMOSOMAL ABNORMALITIES! AL Sciascia, 0 PretoriusX, N BudorickX, T Cahillx, F Axelrocr', G leopold". University of California, San Diego, La Jolla, CA. Sonographic detection of echogenic bowel (EB) in the midtrimester fetus has been associated with cystic fibrosis (CF) and aneuploidy, as well as being a normal variant. From 8/1/90-7/31/91, 22 cases of EB were prospectively detected. Sonograms were performed for the following indications: advanced maternal age(8), tMSAFP(6), lMSAFP(4), anatomic survey(2), and outside stud; es revealing EB (1) and polyhydralTV1ios and EB (1). Gestational age ranged from 15-26 wks, mean 18 wks. Families were counselled regarding the association of EB with CF and aneuploidy and offered testing; 19 arrniocenteses were performed, and 17 chose DNA-based CF risk assessment. Six trisomic fetuses were detected (Trisomy 21 (5) Trisomy 18 (1». No fetus with CF was detected. The diagnosis of EB can be subjective due to technical variabi l ity. Equi~nt, settings and maternal habitus all affect bowel appearance. To determi ne rel i abi l i ty and i nterobserver vari abi l i ty, the 22 cases and 10 randomly selected controls were reviewed by 4 authors and graded as: normal-a, mi ld·1, or bright-2. All agreed on grade (Gr) in 15 cases, 3 of 4 agreed in 14, and in 3 cases the assessment was spl it. In only one case was the disagreement greater than 1 Gr. To further analyze the 22 cases of EB, Gr was assigned by consensus, 10 cases were Gr 2 and 10 cases Gr 1. Two cases were spl i t between mi ld and bright and arbitrari Ly assigned Gr 2, both had normal studies. Of the 12 cases with Gr 2 EB - 5 trisomic fetuses were detected; 1 trisomic fetus was detected in the 10 with Gr 1 EB. Other abnormalities detected prenatally in the trisomic fetuses included - Trisomy 18 -VSD, absent stomach, club feet, clenched hands and renal abnormal ities; Trisomy 21-nuchal thickening (NT) of 5.7 om ('), NT 5,' om and short femur (1), bilateral choroid plexus cysts and NT 4 om (1); no abnormalities detected (2), In 3 trisomic fetuses, pathologic examination of the bowel revealed no gross or microscopic abnormal ities. CF studies revealed no parent or fetus with the delta F508 mutation and the haplotype distribution was unremarkable. A larger series is necessary to determine whether CF testing is efficacious. Conclusion:(1) It appears that interobserver error is sufficientlY small to allow detection of EB. (2) Six of 22 fetuses with EB proved to be trisomic; those with brightly EB were at greatest risk..
21
PREGNANCY LOSS AFTER FIRST TRIMESTER UL TRASONOGRAPHIC DOCUl1ENTATION OF EMBRYONIC/FETAL CARDIAC ACTIVITY. ~effrey'_M. Barrett~ Jennifer Brinson, R.N.C. x, Hatson Clinic, Lakeland, Florida. I A prospective study was performed to evaluate the characteristics of pregnancy loss before 26 weeks when there is first trimester documentation of embryonic/fetal cardiac activity.
Pregnancy dating and documentation of
cardiac activity was performed wi th real time ul trasonography.
Pregnancy losses were evaluated and dated wi th
ul trasonography and/or pathologic macroscopic evaluation of most cases.
A total of 897 consecutive patients were
evaluated wi-th pregnancy outcome known in 99.8%'.
The
overall loss rate after documentation of embryonic/fetal cardiac activity, corrected for elective first trimester termination, was 4.6%', increasing from 10.5%' <7 weeks to 2.2%' >/10 weeks and 1.6% >/15 weeks.
Over half of the
losses occurred before 10 weeks, wi th there being no relationship between maternal age and frequency of loss in this group.
However, with gestational age >/10 weeks,
maternal age was a factor in the frequency of pregnancy loss wi th the total loss rate 1.6%/age 35.
The age related increase in pregnancy loss continued
to be pl~esent when corrected for pregnancies terminated due to chromosomal or severe structural abnormali ties. These findings have important implications regarding the safety of invasive fetal testing and the ~valuation of exogenous factors which may cause fetal loss.
22
EVALUATION OF FETAL BLOOD CONTENT IN TRANSABDOMINAL AND TRANSCERVICAL CHORIONIC VILLUS SAMPLES. K. Blakemore, I. Baser", N. Cellen, R.S. Shirey', T. Kickier", M. Blitzer". The Johns Hopkins Univ. Sch. of Med. and Univ. of Maryland, Balto., MD, The risk of fetal blood loss with first trimester chorionic villus sampling ICVS) has attained renewed importance. Fetal limb reduction abnormalities that appear consistent with a vascular disruptive etiology have raised questions as to whether or not CVS is potentially teratogenic, or whether the technique employed, transcervical (TC) or transabdominal ITAl. matters. To determine how often fetal blood is actually retrieved with CVS, we examined 70 first trimester CVS aspirates, i.e. the blood surrounding the villus tissue, by acid-elution staining for fetal hemoglobin IHbF). Forty aspirates were obtained by TC catheter aspiration, and 30 by TA aspiration using a 20 gauge spinal needle. In 23 cases, pre- and post-procedure maternal serum alpha fetoprotein IMSAFP) levels were obtained 1'6 TC and 7 TA). The percentage of HbF positive cells was",' 0% in 46/70 aspirates 164%). '" 30% in 26170 aspirates 136%). end", 80% in 8 cases 11 , %). All 8 aspirates ~ 80% HbF were obtained transsbdominally. Chi square analysis of TA vs TC aspirates revealed TA aspirates to have a consistently higher %HbF Ip<.02,.006, and .00' respectively). Mean %HbF, TA=43% vs TC= '6%, was also statistically different Ip< .00'). The mean sample size Img of villi) differed between the two groups ITA = '6 mg va TC = 29 mg; p < .00') with TC aspirates appearing more bloody on a scale of 0-4. The T A group had a greater proportion of patients whose MSAFP values increased by > 60%, but this did not reach statistical significance with these small patient numbers. These data suggest that TA CVS may be associated with greater fetal blood spillage; however, the acid elution technique cannot directly quantify fetal blood amount, 8S it varies with the amount of maternal blood present. Our data do provide direct evidence that the integrity of the placenta's fetal vasculature is disrupted to at le88t some degree in the majority of CVS procedures, both TA and TC. A larger study including AFP measurement on CVS aspirates is underway.
283
Volume 166 N umber I, Part 2
19 A PROSPECTIVE EVALUATION OF TRIPLE MARKER
MATERNAL SERUM SCREENING FOR TRISOMY-2l. EY cheng,X DA Luthy, DE Hickok, R Lieppman, RG Resta,X M Williams, x A Zebelman,x F Luthardt,X Swedish HOsp. Med. Ctr., Seattle WA Early data suggest the use of triple marker analysis from maternal serum may be an effective screening tool for the prenatal diagnosis of Trisomy-21. From 1/1/90 to 8/15/91 we evaluated the triple marker screen obtained at 16-18 weeks gestation in singleton, non-diabetic pregnancies, using MSAFP (HYBERTECH), unconjugated estriol, and total HCG (AMERSHAM) as the analytes measured. We defined a midtrimester risk for Trisomy-2l' of ~1:195 as a positive screen. Pilot studies indicated that 7% of pregnancies would be screen-positive and approximately 2/3 of all cases of Trisomy-21 could be detected. During the 20-month study period 7785 pregnancies were tested with a mean maternal age of 29.3±4.8. 572 pregnancies (7.5%) were screen-positive. 298 of the 7785 pregnancies screened (3.8%) eventually underwent amniocentesis, yielding 21 cases of Trisomy-21. Twenty-one of 298 of amniocenteses (PVP=7%) resulted in a diagnosis of Trisomy-21, comparing favorably to amniocenteses for advanced maternal age, in which 1-2% of procedures yield Trisomy-21. The use of 3 markers (MSAFP, HCG, estriol) improved screening performance, compared to MSAFP and HCG without estriol. The data suggest triple marker analysis is an effective prenatal screen for Trisomy-21.
20
MID-TRIMESTER ECHOGENIC BO~EL AND CHROMOSOMAL ABNORMALITIES! AL Sciascia, 0 PretoriusX, N BudorickX, T Cahillx, F Axelrocr', G leopold". University of California, San Diego, La Jolla, CA. Sonographic detection of echogenic bowel (EB) in the midtrimester fetus has been associated with cystic fibrosis (CF) and aneuploidy, as well as being a normal variant. From 8/1/90-7/31/91, 22 cases of EB were prospectively detected. Sonograms were performed for the following indications: advanced maternal age(8), tMSAFP(6), lMSAFP(4), anatomic survey(2), and outside stud; es revealing EB (1) and polyhydralTV1ios and EB (1). Gestational age ranged from 15-26 wks, mean 18 wks. Families were counselled regarding the association of EB with CF and aneuploidy and offered testing; 19 arrniocenteses were performed, and 17 chose DNA-based CF risk assessment. Six trisomic fetuses were detected (Trisomy 21 (5) Trisomy 18 (1». No fetus with CF was detected. The diagnosis of EB can be subjective due to technical variabi l ity. Equi~nt, settings and maternal habitus all affect bowel appearance. To determi ne rel i abi l i ty and i nterobserver vari abi l i ty, the 22 cases and 10 randomly selected controls were reviewed by 4 authors and graded as: normal-a, mi ld·1, or bright-2. All agreed on grade (Gr) in 15 cases, 3 of 4 agreed in 14, and in 3 cases the assessment was spl it. In only one case was the disagreement greater than 1 Gr. To further analyze the 22 cases of EB, Gr was assigned by consensus, 10 cases were Gr 2 and 10 cases Gr 1. Two cases were spl i t between mi ld and bright and arbitrari Ly assigned Gr 2, both had normal studies. Of the 12 cases with Gr 2 EB - 5 trisomic fetuses were detected; 1 trisomic fetus was detected in the 10 with Gr 1 EB. Other abnormalities detected prenatally in the trisomic fetuses included - Trisomy 18 -VSD, absent stomach, club feet, clenched hands and renal abnormal ities; Trisomy 21-nuchal thickening (NT) of 5.7 om ('), NT 5,' om and short femur (1), bilateral choroid plexus cysts and NT 4 om (1); no abnormalities detected (2), In 3 trisomic fetuses, pathologic examination of the bowel revealed no gross or microscopic abnormal ities. CF studies revealed no parent or fetus with the delta F508 mutation and the haplotype distribution was unremarkable. A larger series is necessary to determine whether CF testing is efficacious. Conclusion:(1) It appears that interobserver error is sufficientlY small to allow detection of EB. (2) Six of 22 fetuses with EB proved to be trisomic; those with brightly EB were at greatest risk..
21
PREGNANCY LOSS AFTER FIRST TRIMESTER UL TRASONOGRAPHIC DOCUl1ENTATION OF EMBRYONIC/FETAL CARDIAC ACTIVITY. ~effrey'_M. Barrett~ Jennifer Brinson, R.N.C. x, Hatson Clinic, Lakeland, Florida. I A prospective study was performed to evaluate the characteristics of pregnancy loss before 26 weeks when there is first trimester documentation of embryonic/fetal cardiac activity.
Pregnancy dating and documentation of
cardiac activity was performed wi th real time ul trasonography.
Pregnancy losses were evaluated and dated wi th
ul trasonography and/or pathologic macroscopic evaluation of most cases.
A total of 897 consecutive patients were
evaluated wi-th pregnancy outcome known in 99.8%'.
The
overall loss rate after documentation of embryonic/fetal cardiac activity, corrected for elective first trimester termination, was 4.6%', increasing from 10.5%' <7 weeks to 2.2%' >/10 weeks and 1.6% >/15 weeks.
Over half of the
losses occurred before 10 weeks, wi th there being no relationship between maternal age and frequency of loss in this group.
However, with gestational age >/10 weeks,
maternal age was a factor in the frequency of pregnancy loss wi th the total loss rate 1.6%
The age related increase in pregnancy loss continued
to be pl~esent when corrected for pregnancies terminated due to chromosomal or severe structural abnormali ties. These findings have important implications regarding the safety of invasive fetal testing and the ~valuation of exogenous factors which may cause fetal loss.
22
EVALUATION OF FETAL BLOOD CONTENT IN TRANSABDOMINAL AND TRANSCERVICAL CHORIONIC VILLUS SAMPLES. K. Blakemore, I. Baser", N. Cellen, R.S. Shirey', T. Kickier", M. Blitzer". The Johns Hopkins Univ. Sch. of Med. and Univ. of Maryland, Balto., MD, The risk of fetal blood loss with first trimester chorionic villus sampling ICVS) has attained renewed importance. Fetal limb reduction abnormalities that appear consistent with a vascular disruptive etiology have raised questions as to whether or not CVS is potentially teratogenic, or whether the technique employed, transcervical (TC) or transabdominal ITAl. matters. To determine how often fetal blood is actually retrieved with CVS, we examined 70 first trimester CVS aspirates, i.e. the blood surrounding the villus tissue, by acid-elution staining for fetal hemoglobin IHbF). Forty aspirates were obtained by TC catheter aspiration, and 30 by TA aspiration using a 20 gauge spinal needle. In 23 cases, pre- and post-procedure maternal serum alpha fetoprotein IMSAFP) levels were obtained 1'6 TC and 7 TA). The percentage of HbF positive cells was",' 0% in 46/70 aspirates 164%). '" 30% in 26170 aspirates 136%). end", 80% in 8 cases 11 , %). All 8 aspirates ~ 80% HbF were obtained transsbdominally. Chi square analysis of TA vs TC aspirates revealed TA aspirates to have a consistently higher %HbF Ip<.02,.006, and .00' respectively). Mean %HbF, TA=43% vs TC= '6%, was also statistically different Ip< .00'). The mean sample size Img of villi) differed between the two groups ITA = '6 mg va TC = 29 mg; p < .00') with TC aspirates appearing more bloody on a scale of 0-4. The T A group had a greater proportion of patients whose MSAFP values increased by > 60%, but this did not reach statistical significance with these small patient numbers. These data suggest that TA CVS may be associated with greater fetal blood spillage; however, the acid elution technique cannot directly quantify fetal blood amount, 8S it varies with the amount of maternal blood present. Our data do provide direct evidence that the integrity of the placenta's fetal vasculature is disrupted to at le88t some degree in the majority of CVS procedures, both TA and TC. A larger study including AFP measurement on CVS aspirates is underway.
283