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246 Identification of Turner Syndrome with Fetal Hydrops in Multiple Marker Screening for Down Syndrome
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244
spa Abstracts
SIMILARITY OFlWINS TO SINGLETON MSAFP RATIO BY RACE: NO NEED TO ESTABlISHSPECIAC MULTI FETAL TABLES. AJlrJIswl,x JE O'Brien, R Gambino, MP Johnson~MI Evans, Depts ObIGyn, Hutzel HospitalWayne State U, Detroit, MI, Rambam Medical Center, Haifa, Israel, and MetPath Inc., Teterboro, NJ MSAFP values in 535 twin gestations were grouped according to week of gestation (15·20 wks) and race. MSAFP (MIU/ml) in blacks was higher than in whites (p<.01). Wh~e Pregnancies Black Pregnancies
January 1992 Am J Obstet Gynecol
246
IDENTIFICATION OF TIJRNER SYNDROME WITIi FETAL HYDROPS IN MULTIPLE MARKER SCREENING FOR DOWN SYNDROME D N Saller Jrl , M G Blltzer2x , S Schwartz 2x & J A Canick1x IBrown Unlv./Women & Infants Hosp, Prov.. RI & 2DIv. of Human Genetics. Unlv. of Md. at Baltimore, MD We previously reported the Identification of non-Immune fetal hydrops, some cases of which had Turner syndrome, tn multiple marker screentng for Down syndrome (which Is based on age, lowalpha-fetoprotetn [AFP). low unconjugated estriol [uE3) & elevated human chOrionic gonadoiropln [hCGIJ. These cases were detected because of conSistently low uE3 & markedly elevated hCG. In order to Investigate the levels of uE3, hCG. & AFP associated with Turner syndrome, we Identified 15 cases of 45,X karyolypes (7 with hydrops and 8 without) for which a second trimester maternal serum sample was available. The AFP levels were reduced tn both groups (median MoM=0.81, range=0.39-1.59). although 4 of these cases had been referred for low AFP (possibly blastng the AFP levels). The uE3 levels were substantially reduced tn both groups (median MoM=O.48, range=0.12-1.45). The hCG levels had a bimodal distribution with no overlap (rank sum test, p=O.OOI), tn which all 7 hydropic pregnancies had markedly elevated levels (median MoM=3.84, range= 1. 80-5. 77) and all 8 non-hydropiC pregnancies had low levels (median MoM=0.52. range=0.21-0.76). All of the 7 hydropiC cases would have been Identified as screen positive for Increased Down syndrome risk while none of the 8 non-hydropic cases would have been so Identified. These findtngs tndicate that the morpholologlc defect of hydrops fetalls. rather than the 45,X karyolype Itself, is responsible for the high risk pattern In multiple marker screening for Down syndrome. Nonhydropic 45,X pregnancies have relatively low AFP. uE3 & hCG, and are unlikely to be Identified as high risk for Down syndrome. They may, however, be detected as high risk for Trisomy 18 (in which all 3 markers are consistently low).
247
PRENATAL ALCOHOL EXPOSURE AND NEUROBEHAVIORAL FUNCTION IN INFANCY: EVIDENCE FOR THRESHOLD AND DIFFERENTIAL VULNERABILITY. J.L. Jacobson,' S.W. Jacobson,' R.J. Sokol, S.S. Martier,' J.W. Ager,' Depts Ob/Gyn and Psychology and Fetal Alcohol Research Center, Wayne State Univ., Detroit, MI The relation of prenatal alcohol exposure to anatomic alcohol-related birth defects (arbdl has been characterized in our studies as exhibiting a threshold and differential fetal vulnerability. Though relations of prenatal exposure to neurobehavioral abnormality have been reported, threshold effects and differential vulnerability have not been systematically sought. In a prospectively studied disadvantaged inner city black sample (n =3891, periconceptional and antepartum fetal alcohol exposure was estimated from repeated maternal reports and the Bayley scales of infant development administered to offspring at age 1 year by examiners blinded to prenatal history. Consistent with previous studies, after control for potential confounders, higher levels of drinking at conception and during pregnancy were associated with poorer performance on the Bayley with no evidence of threshold. However, when 1 standard deviation below the sample mean was used as the criterion for poor performance, no effect was detectable below 14 oz of absolute alcohol per week (AAIWI (28 standard drinks/wi periconceptionally or 3.5 oz AAIW (7 drinks/wi during pregnancy. Using this criterion, neurobehavioral function was notably impaired in 30% of the higher exposed offspring, but not in the remaining 70%. These results suggest that, as with anatomic arbd, relationships of prenatal alcohol exposure to neurobehavioral abnormality may be characterized by a threshold above which there are marked individual differences in vulnerability to the effects of prenatal alcohol exposure.
No. Twins Single Ratio No. Twins Single Ratio 2.18 81 56.8 26.1 2.17 19 56.3 25.8 77.6 30.8 2.52 2.14 17C 60.6 28.3 33 83.4 33.2 2.51 2.16 101 69.9 32.3 25 1.96 50 74.7 38.0 1.97 18 85.1 45.1 88.0 48.1 1.83 16 83.2 43.1 1.93 6 10 107.5 44.4 2.42 6 96.5 56.7 1.70 210 Iota! 428 213 107 Using J:al:II. ~ cutoffs of 4.5 MOM, 3.7% of whites and 4.7% of blacks were considered high, which is comparable to findings in singletons. These differences would not have been found in a non· adjusted mixed race database. "Low" results (1.0 MOM for age· matched singletons) were seen in 7.2% of whites and 5.6% of blacks, comparable to singleton pregnancies. Using race·specific databases, the interracial differences in frequency of either "high" or "low" results was not significant. We conclude: 1) different databases should be used in black and white twin pregnancies, 2) "High" (>4.5 MOM) and "low" (<1 MOM) cutoff values derived from the large databank of singleton pregnancies seem to be adequate for interpretation of MSAFP results in twins, obviating the need to build specific median curves for multifetal gestations. GA 15 16 17 18 19 20
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FETAL CHOROID PLEXUS CYSTS: THE SHALL 0:( TP.All-· SIENT CYST IS NOT NECESSARILY BENIGN. V, Klein, M, Perpignan.0, H, Cohen~ F. l1andel~ J. Streltzhoff~ F. Chervenak, Depts, Ob/Gyn, Radi-· ology and Research, North Shore Univ. Hosp. and NY Hosp., Cornell Univ. !-fed. College, NY Analysis of 3770 obstetrical patients having prenatal sonograms between 14 and 32 wks. gestation revealed that 87(2.3%) were found to have fetal choroid plexus cysts, Eighty-three patients underwent amniocentesis, six(7.2~) had abnormal karyotypes. Four cases had the common-' ly associated chromosomal abnormality, trisomy 18. Two cases had a karyotype not usually asso-' ciated with choroid plexus cysts, mosaic Turner's and trisomy 21. Of the six abnormal karyotypes, one had a 4 mm unilateral cyst, and 3 had bilateral cysts of 3-5 mm; two had larger cysts. In only one case with a 16 mm cyst had any associated structural abnormalities been detected sonographically. In the two cases of trisomy 18 that were not terminated and in the fetuses with trisomy 21 and mosaic Turner, cysts resolved between 23-26 wks. Our data suggests that fetal karyotyping should be considered in all fetuses with choroid plexus cysts, irregardless of laterality, size or spontaneous resolution prior to birth.
244
spa Abstracts
SIMILARITY OFlWINS TO SINGLETON MSAFP RATIO BY RACE: NO NEED TO ESTABlISHSPECIAC MULTI FETAL TABLES. AJlrJIswl,x JE O'Brien, R Gambino, MP Johnson~MI Evans, Depts ObIGyn, Hutzel HospitalWayne State U, Detroit, MI, Rambam Medical Center, Haifa, Israel, and MetPath Inc., Teterboro, NJ MSAFP values in 535 twin gestations were grouped according to week of gestation (15·20 wks) and race. MSAFP (MIU/ml) in blacks was higher than in whites (p<.01). Wh~e Pregnancies Black Pregnancies
January 1992 Am J Obstet Gynecol
246
IDENTIFICATION OF TIJRNER SYNDROME WITIi FETAL HYDROPS IN MULTIPLE MARKER SCREENING FOR DOWN SYNDROME D N Saller Jrl , M G Blltzer2x , S Schwartz 2x & J A Canick1x IBrown Unlv./Women & Infants Hosp, Prov.. RI & 2DIv. of Human Genetics. Unlv. of Md. at Baltimore, MD We previously reported the Identification of non-Immune fetal hydrops, some cases of which had Turner syndrome, tn multiple marker screentng for Down syndrome (which Is based on age, lowalpha-fetoprotetn [AFP). low unconjugated estriol [uE3) & elevated human chOrionic gonadoiropln [hCGIJ. These cases were detected because of conSistently low uE3 & markedly elevated hCG. In order to Investigate the levels of uE3, hCG. & AFP associated with Turner syndrome, we Identified 15 cases of 45,X karyolypes (7 with hydrops and 8 without) for which a second trimester maternal serum sample was available. The AFP levels were reduced tn both groups (median MoM=0.81, range=0.39-1.59). although 4 of these cases had been referred for low AFP (possibly blastng the AFP levels). The uE3 levels were substantially reduced tn both groups (median MoM=O.48, range=0.12-1.45). The hCG levels had a bimodal distribution with no overlap (rank sum test, p=O.OOI), tn which all 7 hydropic pregnancies had markedly elevated levels (median MoM=3.84, range= 1. 80-5. 77) and all 8 non-hydropiC pregnancies had low levels (median MoM=0.52. range=0.21-0.76). All of the 7 hydropiC cases would have been Identified as screen positive for Increased Down syndrome risk while none of the 8 non-hydropic cases would have been so Identified. These findtngs tndicate that the morpholologlc defect of hydrops fetalls. rather than the 45,X karyolype Itself, is responsible for the high risk pattern In multiple marker screening for Down syndrome. Nonhydropic 45,X pregnancies have relatively low AFP. uE3 & hCG, and are unlikely to be Identified as high risk for Down syndrome. They may, however, be detected as high risk for Trisomy 18 (in which all 3 markers are consistently low).
247
PRENATAL ALCOHOL EXPOSURE AND NEUROBEHAVIORAL FUNCTION IN INFANCY: EVIDENCE FOR THRESHOLD AND DIFFERENTIAL VULNERABILITY. J.L. Jacobson,' S.W. Jacobson,' R.J. Sokol, S.S. Martier,' J.W. Ager,' Depts Ob/Gyn and Psychology and Fetal Alcohol Research Center, Wayne State Univ., Detroit, MI The relation of prenatal alcohol exposure to anatomic alcohol-related birth defects (arbdl has been characterized in our studies as exhibiting a threshold and differential fetal vulnerability. Though relations of prenatal exposure to neurobehavioral abnormality have been reported, threshold effects and differential vulnerability have not been systematically sought. In a prospectively studied disadvantaged inner city black sample (n =3891, periconceptional and antepartum fetal alcohol exposure was estimated from repeated maternal reports and the Bayley scales of infant development administered to offspring at age 1 year by examiners blinded to prenatal history. Consistent with previous studies, after control for potential confounders, higher levels of drinking at conception and during pregnancy were associated with poorer performance on the Bayley with no evidence of threshold. However, when 1 standard deviation below the sample mean was used as the criterion for poor performance, no effect was detectable below 14 oz of absolute alcohol per week (AAIWI (28 standard drinks/wi periconceptionally or 3.5 oz AAIW (7 drinks/wi during pregnancy. Using this criterion, neurobehavioral function was notably impaired in 30% of the higher exposed offspring, but not in the remaining 70%. These results suggest that, as with anatomic arbd, relationships of prenatal alcohol exposure to neurobehavioral abnormality may be characterized by a threshold above which there are marked individual differences in vulnerability to the effects of prenatal alcohol exposure.
No. Twins Single Ratio No. Twins Single Ratio 2.18 81 56.8 26.1 2.17 19 56.3 25.8 77.6 30.8 2.52 2.14 17C 60.6 28.3 33 83.4 33.2 2.51 2.16 101 69.9 32.3 25 1.96 50 74.7 38.0 1.97 18 85.1 45.1 88.0 48.1 1.83 16 83.2 43.1 1.93 6 10 107.5 44.4 2.42 6 96.5 56.7 1.70 210 Iota! 428 213 107 Using J:al:II. ~ cutoffs of 4.5 MOM, 3.7% of whites and 4.7% of blacks were considered high, which is comparable to findings in singletons. These differences would not have been found in a non· adjusted mixed race database. "Low" results (1.0 MOM for age· matched singletons) were seen in 7.2% of whites and 5.6% of blacks, comparable to singleton pregnancies. Using race·specific databases, the interracial differences in frequency of either "high" or "low" results was not significant. We conclude: 1) different databases should be used in black and white twin pregnancies, 2) "High" (>4.5 MOM) and "low" (<1 MOM) cutoff values derived from the large databank of singleton pregnancies seem to be adequate for interpretation of MSAFP results in twins, obviating the need to build specific median curves for multifetal gestations. GA 15 16 17 18 19 20
245
FETAL CHOROID PLEXUS CYSTS: THE SHALL 0:( TP.All-· SIENT CYST IS NOT NECESSARILY BENIGN. V, Klein, M, Perpignan.0, H, Cohen~ F. l1andel~ J. Streltzhoff~ F. Chervenak, Depts, Ob/Gyn, Radi-· ology and Research, North Shore Univ. Hosp. and NY Hosp., Cornell Univ. !-fed. College, NY Analysis of 3770 obstetrical patients having prenatal sonograms between 14 and 32 wks. gestation revealed that 87(2.3%) were found to have fetal choroid plexus cysts, Eighty-three patients underwent amniocentesis, six(7.2~) had abnormal karyotypes. Four cases had the common-' ly associated chromosomal abnormality, trisomy 18. Two cases had a karyotype not usually asso-' ciated with choroid plexus cysts, mosaic Turner's and trisomy 21. Of the six abnormal karyotypes, one had a 4 mm unilateral cyst, and 3 had bilateral cysts of 3-5 mm; two had larger cysts. In only one case with a 16 mm cyst had any associated structural abnormalities been detected sonographically. In the two cases of trisomy 18 that were not terminated and in the fetuses with trisomy 21 and mosaic Turner, cysts resolved between 23-26 wks. Our data suggests that fetal karyotyping should be considered in all fetuses with choroid plexus cysts, irregardless of laterality, size or spontaneous resolution prior to birth.