Volume 168 Number 1, Part 2

373 EFFECT OF FETAL GENDER ON THE PREDICTION OF DOWN SYNDROME. C J Lockwood, L. Lynch, A. Ghidinix, G.

Berkow~z, R. Lapinski, W. Miller". MI. Sinai School of Med, NY, NY. OBJECTIVE: A cohort study was undertaken to determine whether fetal gender affected the prediction of fetal Down syndrome (OS) using second trimester sonography and MSAFP values. STUDY DESIGN: Data on maternal age, MSAFP, and fetal biometric parameters were recorded at the time of genetic amniocentesis. Fetuses w~h anatomic and non-OS chromosomal anomalies were excluded. Gender-specific variations in sonographic parameters and MSAFP levels were analyzed in 42 DS and 4949 euploid fetuses. Receiver-operator Characteristic curve analysis was then used to determine which of gender-specific sonographic parameters produced the optimal sensitivity (sens.) for a specificity> 95%. RESULTS: No gender-related differences were observed for nuchal fold thickness (NFT) in e~her euploid or OS fetuses and a NFT ~ 5 mm was the best individual gender-independent predictor of fetal OS [sens.: 29.4% (95% CI:14.1,44.7]. Compared w~h the euploid population, humeral (HL) and femoral (FL) lengths w~h or w~hout adjustment for biparietal diameter (BPO) were significantly shorter in male but not female OS fetuses. Similarly, deviation in the ohserved-minus-expected HL adjusted for BPO was predictive of OS only among male fetuses [sens.: females - 16.7% (-4.4,37.8); males _ 44.4% (12.0,76.9)). In contrast to these biometric findings, MSAFP values were reduced in patients w~h female but not male DS fetuses [0.76 (±0.3) vs. 1.0 MOM (±0.3)). No correlations were found between maternal age, MSAFP levels, NFT, FL and HL. Indeed, the presence of e~her a NFT ~ 6 mm or an observed-minus­expected HL < 3.6 mm maximally predicted OS in male fetuses [sens.: females - 41.7% (13.8,69.6); males - 62.5% (29.0,96.0)]. CONCLUSION: While MSAFP appears to be a better screening test for female OS fetuses, sonographic parameters are a better predictor of OS among male fetuses.

374 PRENATAL DIAGNOSIS OF A PARTIAL TRISOMY THROUGH IN SITU HYBRIDIZATION ON AMNIOCYTES WITH WHOLE CHROMOSOME AND CENTROMERE SPECIFIC DNA PROBES. I BlancatoX, G Eglinton. T Pinckert, I Benkendorf, I Meckx. Dept. Ob,Gyn, Georgetown University, Washington, DC. OBJECTIVE: This report shows the importance of using DNA probes as adjuncts to standard cytogenetic analysis when a marker chromosome of unknown origin is identified. STUDY DESIGN: Amniocentesis performed on a 29 year old primigravida evaluated at 35 weeks' gestation for low fundal height with fOldings of fetal growth retardation and diaphragmatic hernia, showed the presence of a small, supernumerary acrocentric marker chromosome in all cells by means of G-banding. Because of the uncertain origin of the marker chromosome, molecular cytogenetic studies were employed to aid in identification of the marker chromosome. Metaphase spreads were subsequently analyzed by means of florescent in situ hybridization using a centromere probe specific for chromosome 22 and a whole chromosome probe for the II chromosome. Parental blood cytogenetic and in situ hybridization studies were also performed using the same probes. RESULTS: In situ hybridization showed that the marker chromosome was a derivative of chromosome 22 with Ilq material attached near the centromere. The fetal karyotype was 47,XY,+<Ier(22)t(11 ;22) (q23.3;qI1.2). Parental chromosome analysis by means of DNA probes revealed that the mother carried a balanced 11;22 translocation. More than ISO cases of the same translocation have been ascertained through malformed offspring with unbalanced translocation or history of infertility in the balanced carrier (Fraccaro et al., 1980; Zackai and Emmanual, 1980; Schinzel et al., 1981). The phenotype in unbalanced offspring is well described and includes complex heart defects, renal anomalies and diaphragmatic hernia. CONCLUSIONS: DNA probes specific for whole chromosomes or centromeres are invaluable tools in the accurate determination of unbalanced karyotypes in prenatal diagnosis and provide important information to aid the clinician in pregnancy management and the geneticist in relaying accurate recurrence risk information to the patient.

SPO Abstracts 401

375 Medium Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency Is Predicted by Elevated Serum Dodecanoic Acid (SDA). B.B. Little: P.M. Kemp: R.O. Bost: Depts. of Ob/Gyn and Pathology, UT Southwestern Medical Ctr., Dallas, TX, and Dept. of Pharmacology, LSU Medical Ctr., Shreveport, LA.

376

OBJECTIVE: Previously, we found that 5.3% of 57 sudden infant death syndrome (SIDS) cases had SDA levels ~ the 99th percentile (19.4 mg/L) of control values. In this study, we investigated whether or not elevated SDA was due to a p­oxidation defect In fatty acid metabolism In a different cohort. STUDY DESIGN: We prospectively analyzed blood and urine from 55 consecutive SIDS cases for fatty acids by gas chromatography/mass spectrometry (GC/MS). RESULTS: Three of 55 cases had elevated SOA concentra­tions. Urlnes from these three cases along with 25 urines from SIOS cases with normal SDA concentrations (-7mg/L) were submitted to outside laboratories for confirmation of MCAD deficiency by GC/MS of organic acids and acyl-glycines. The three with elevated SDA were confirmed MCAD deficient. CONCLUSION: Elevated SDA is highly specific for predicting MCAD deficiency in SIOS victims. SDA is eas~y seen in routine toxicology done at autopsy. MCAD deficiency is autosomal recessive, carrying a 25% recurrence risk. Hence, gravidas who gave birth to a SIDS victim with elevated SDA should be advised of prenatal and perinatal diagnOSis of MCAD deficiency because it can be treated and prevent sudden, unexplained infant deaths of subsequent offspring.

MULTI-ALLELE DNA ANALYSIS OF FETAL CELLS ISOLA­TED FROM MATERNAL PERIPHERAL BLOOD. D. Schmid t· • J Leary*, Camille DallaTorreo, J Gram*, and Stefan Burde*. Dept. Gyn-Ob, SUNY at Buffaloo, Dept. Path. J U of Rochester, Rochester. NY*. OBJECTIVE: To show that multi-allele DNA analysis of single fetal cells may be used for verification of the isolation of fetal cells from maternal blood. STUDY DESIGN: In 10 patients undergoing first tri­mester prenatal diagnosis J single cells from ma­ternal, paternal, & fetal control specimens were isolated using a "cookie cutterl! method. Flow cy­tome try was used to isolate single fetal nucleated RBC I S from maternal blood drawn prior to the pre­natal diagnosis procedure. Control specimens from all investigators were also obt-ained. Primers for the group specific component gene were added to the Amplitype HLA-DQI'< system. 40 cycles of PCR were used on each vial containing a single nucleated RBC or control maternal, paternal, and fetal specimens. RESULTS: Amplified single cells from all the control specimens showed alleles for the HLA-DQo< and group specific component genes. In some of the single cell PCR reactions of fetal nucleated RBC's, a paternal specific allele was identified. These PCR products also contained a Single maternal allele and no apparent contaminant alleles from researchers. CONCLUSIONS: This technique has advantages over other published me thods for documentation of isola­ted fetal cells using Y-allele DNA analysis and FISH. Both male and female fetal cells and/or normal diploid fetal cells can be identified. Multi-allele single cell analysis gives the equiva­lent of pure fetal specimens, since maternal cells or researcher contaminants are eliminated. False positives from FISH and Y-allele peR are eliminated.