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J L Simpson

Publications and source records attributed to J L Simpson.

At least 19 recordsLinked to original sources
PubMed1992

A randomized comparison of transcervical and transabdominal chorionic-villus sampling. The U.S. National Institute of Child Health and Human Development Chorionic-Villus Sampling and Amniocentesis Study Group.

BACKGROUND: Chorionic-villus sampling is done in early pregnancy to obtain fetal cells for the prenatal diagnosis of genetic and chromosomal defects. Transcervical chorionic-villus sampling has been shown to be safe and effective in national trials. Recently, an alternative transabdominal technique has been suggested as potentially easier and safer. METHODS: From April 1987 through September 1989, we prospectively compared transcervical and transabdominal chorionic-villus sampling in 3999 women with singleton pregnancies in whom the risk of a genetically abnormal fetus was increased. Women between 7 and 12 weeks of gestation underwent ultrasonographic evaluation of placental and uterine position. Those with active vaginal infections, active bleeding, or cervical polyps were excluded. If the obstetrician thought either sampling procedure was acceptable, the woman was asked to consent to random assignment to one of the two procedures. Both groups were followed to determine the outcome of pregnancy and the rate of spontaneous fetal loss after chorionic-villus sampling. RESULTS: Among the 3999 women who entered the study, sampling was attempted in 3873 (97 percent), 1944 of whom had been assigned to undergo transcervical sampling and 1929 to undergo transabdominal sampling. Of these 3873 women, sampling was eventually successful in 3863. Sampling was successful after a single insertion of the sampling instrument in 94 percent of the transabdominal procedures and 90 percent of the transcervical procedures. Among the women with cytogenetically normal pregnancies who had sampling because of maternal age, the rate of spontaneous fetal loss through 28 weeks of pregnancy was 2.5 percent in the transcervical-sampling group and 2.3 percent in the transabdominal-sampling group (difference, 0.26 percent; 95 percent confidence interval, -0.5 to 1.0 percent). CONCLUSIONS: Transabdominal and transcervical chorionic-villus sampling appear to be equally safe procedures for first-trimester diagnosis of fetal abnormalities.

Abdomen↗
PubMed1992

Transvaginal chorionic villus sampling using transabdominal ultrasound guidance.

Transvaginal chorionic villus sampling (CVS) using concurrent transabdominal ultrasound guidance was performed in six women who desired CVS but could not be offered transcervical or transabdominal approaches because of uterine position and placental location. Satisfactory amounts of chorionic villi were obtained in all six cases with no maternal discomfort, an occurrence that contrasts with our experience in transvaginal CVS using endovaginal ultrasound guidance. We believe that transvaginal CVS using concurrent transabdominal ultrasound guidance warrants consideration as an alternative technique for first-trimester CVS in selected patients.

Adult↗
PubMed1992

Cytogenetic results from the U.S. Collaborative Study on CVS.

Cytogenetic data are presented for 11,473 chorionic villus sampling (CVS) procedures from nine centres in the U.S. NICHD collaborative study. A successful cytogenetic diagnosis was obtained in 99.7 per cent of cases, with data obtained from the direct method only (26 per cent), culture method only (42 per cent), or a combination of both (32 per cent). A total of 1.1 per cent of patients had a second CVS or amniocentesis procedure for reasons related to the cytogenetic diagnostic procedure, including laboratory failures (27 cases), maternal cell contamination (4 cases), or mosaic or ambiguous cytogenetic results (98 cases). There were no diagnostic errors involving trisomies for chromosomes 21, 18, and 13. For sex chromosome aneuploidies, one patient terminated her pregnancy on the basis of non-mosaic 47,XXX in the direct method prior to the availability of results from cultured cells. Subsequent analysis of the CVS cultures and fetal tissues showed only normal female cells. Other false-positive predictions involving non-mosaic aneuploidies (n = 13) were observed in the direct or culture method, but these cases involved rare aneuploidies: four cases of tetraploidy, two cases of trisomy 7, and one case each of trisomies 3, 8, 11, 15, 16, 20, and 22. This indicates that rare aneuploidies observed in the direct or culture method should be subjected to follow-up by amniocentesis. Two cases of unbalanced structural abnormalities detected in the direct method were not confirmed in cultured CVS or amniotic fluid. In addition, one structural rearrangement was misinterpreted as unbalanced from the direct method, leading to pregnancy termination prior to results from cultured cells showing a balanced, inherited translocation. False-negative results (n = 8) were observed only in the direct method, including one non-mosaic fetal abnormality (trisomy 18) detected by the culture method and seven cases of fetal mosaicism (all detected by the culture method). Mosaicism was observed in 0.8 per cent of all cases, while pseudomosaicism (including single trisomic cells) was observed in 1.6 per cent of cases. Mosaicism was observed with equal frequency in the direct and culture methods, but was confirmed as fetal mosaicism more often in cases from the culture method (24 per cent) than in cases from the direct method (10 per cent). The overall rate of maternal cell contamination was 1.8 per cent for the culture method, but there was only one case of incorrect sex prediction due to complete maternal cell contamination which resulted in the birth of a normal male.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Chorionic mosaicism: association with fetal loss but not with adverse perinatal outcome.

Cytogenetic data from the United States NICHD collaborative study of chorionic villus sampling (CVS) were used to evaluate the clinical significance of chorionic mosaicism. The 10,754 patients with normal cytogenetic results were compared with 108 patients (1.0 per cent) with placental mosaicism and 181 patients (1.6 per cent) with pseudo-mosaicism. Of the pregnancies intended to continue, the pregnancy loss rate was significantly greater in patients with placental mosaicism than in the cytogenetically normal cohort (8.6 vs. 3.4 per cent, p less than 0.05). However, there was no difference in the frequencies of abruptio placenta, preterm labour or delivery, small-for-gestational-age newborns, pregnancy-induced hypertension, or neonates with Apgar scores less than 7.

Abortion, Spontaneous↗
PubMed1992

First-trimester biochemical and molecular diagnoses using chorionic villi: high accuracy in the U.S. collaborative study.

The accuracy of biochemical and molecular prenatal diagnoses using chorionic villi as the fetal source was assessed by seven centres participating in the NICHD collaborative study on the safety and accuracy of chorionic villus sampling (CVS) and amniocentesis. Of 601 pregnancies studied, biochemical methods were used to determine the diagnosis in 283 fetuses at risk for 35 different metabolic disorders. Fifteen different lysosomal storage diseases accounted for 81 per cent of the biochemical prenatal diagnoses performed, with 57 per cent of these pregnancies at risk for Tay-Sachs disease. No errors were made in the biochemical diagnoses that predicted affected or unaffected fetuses. However, the diagnoses of certain disorders (e.g., mucopolysacchariodosis type IH, metachromatic leukodystrophy, and Krabbe disease) occasionally required confirmatory studies in cultured amniocytes because the enzyme results were inconclusive in direct and/or cultured villi or due to the presence of a pseudodeficiency allele. Of these, only the diagnosis of a fetus at risk for Krabbe disease remained inconclusive after special studies to discriminate between mutant and pseudo-deficiency alleles. Recombinant DNA techniques were used to predict the diagnosis of 318 fetuses at risk for 16 different disorders in which the defective disease gene could be detected either directly or by linkage analysis to a nearby polymorphic marker. Of these, 32 per cent were for haemoglobinopathies, 25 per cent for cystic fibrosis, 24 per cent for Duchenne or Becker muscular dystrophy, and 7 per cent for haemophilias. Pregnancies at risk for known disorders with specific molecular lesions (e.g., sickle cell disease) were accurately diagnosed in direct and/or cultured villi. Diagnoses requiring analyses with closely linked polymorphic markers were occasionally uniformative or inconclusive. Maternal contamination was not reported in any biochemical or molecular-based diagnosis. These studies document the high accuracy and rapidity of both biochemical and mutation-specific prenatal diagnoses with direct and cultured chorionic villi.

Adult↗
PubMed1992

Risk factors associated with transcervical CVS losses.

Factors found to be associated with pregnancy loss after transcervical CVS were race (higher for non-white), history of spontaneous abortion, unplanned pregnancy, history of spotting or bleeding during the pregnancy prior to CVS, and placental position (higher for fundal or lateral locations). Whether the increase in loss risk is due to the factor, per se, or the factor plus the CVS cannot be determined due to the lack of appropriate control data.

Adult↗
PubMed1992

Mutations in the conserved domain of SRY are uncommon in XY gonadal dysgenesis.

In order to evaluate the role of SRY in the determination of the testis, we sequenced the conserved domain of the SRY gene in 8 patients with 46,XY gonadal dysgenesis and 3 patients with related disorders, and compared our data with those obtained in 6 other similar studies. In our study, a 609-bp fragment of SRY was amplified by the polymerase chain reaction and the internal conserved motif was sequenced. SRY sequences did not differ from those in normal males in any of our patients. Overall, 5 de novo mutations have been identified among 56 patients with sporadic XY gonadal dysgenesis (8.9%), and 2 de novo mutations have been identified among 18 patients with related conditions (11%). The unexpectedly low frequency of mutations within the SRY conserved domain in these patients could be caused by undetected Y-linked mutations outside the conserved domain in regions that control transcription during development (e.g., promoter/enhancer regions) or to downstream mutations in other sex-determining genes that need not map to the Y.

Adolescent↗
PubMed1992

Unexplained elevated maternal serum alpha-fetoprotein is not predictive of adverse perinatal outcome in an indigent urban population.

OBJECTIVE: The null hypothesis of this study is that in an urban, indigent obstetric population at high risk for adverse perinatal outcome, unexplained elevations of maternal serum alpha-fetoprotein are not an additional predictor of adverse perinatal outcome. STUDY DESIGN: Perinatal outcomes of 72 patients from a clinic for indigent patients with unexplained elevated maternal serum alpha-fetoprotein levels were compared with those of matched controls from the same population with normal maternal serum alpha-fetoprotein levels. Subjects and controls were matched for age, race, parity, and presence or absence of Hollister risk factors. The frequency of adverse perinatal outcome in the two groups was subjected to matched-pair chi 2 analysis. RESULTS: Adverse perinatal outcome occurred in 38.9% (28 of 72) of subjects with unexplained elevated maternal serum alpha-fetoprotein levels greater than or equal to 2.5 multiples of the median, compared with 31.9% (23 of 72) of controls with normal maternal serum alpha-fetoprotein levels (p = 0.5). No statistically significant difference in adverse perinatal outcomes was found. CONCLUSIONS: Elevated maternal serum alpha-fetoprotein levels offer little if any additional predictive value for adverse perinatal outcome in populations already at high risk for such outcomes on the basis of obstetric or socioeconomic criteria.

Adolescent↗
PubMed1992

The de Watteville Memorial Lecture: reproductive technologies and genetic advances in obstetrics and gynecology.

Public fascination with genetics and the new reproductive technologies seem ubiquitious. Although interest in genetic causation for diseases is not new, attention is increasing. There are several predictable reasons for this. One is the overall decrease in deaths due to infection. As a result, genetic factors producing birth defects loom relatively larger. This is also coupled with the public's increased desire for the ideal pregnancy, especially given a decreased population rate. Finally, the public's appetite is whetted by the increasing number of heritable diseases whose molecular basis is being elucidated. We shall focus on three general areas in which genetic technology increasingly impacts upon the obstetrician/gynecologist: genetics of pregnancy losses, genetics of sex determination and the common gynecologic disorders, and finally prenatal genetic diagnosis, particularly in preimplantation genetics and recovering fetal cells from maternal blood. Most of these topics are discussed in a recent text, where extensive references are available.

Abortion, Spontaneous↗
PubMed1992

Endometrial adenocarcinoma: genetic analysis suggesting heritable site-specific uterine cancer.

UNLABELLED: Genetic factors are clearly integral to the etiology of neoplasia. A cancer family syndrome (Lynch syndrome II) consisting of uterine, colon, and ovarian cancer is recognized, but the heritability of isolated endometrial adenocarcinoma has not otherwise been thoroughly investigated. We have performed pedigree studies in index cases with endometrial adenocarcinoma, using spouses as controls. Preliminary results from 64 probands showed four families in which endometrial adenocarcinoma was diagnosed in at least one first-degree relative of the proband (mother, daughter, sister); none showed relatives with colon or ovarian cancer. In none of the 34 control pedigrees did either a mother or sister have endometrial adenocarcinoma. In four other families, multiple first- and second-degree relatives of probands had adenocarcinoma of the uterus, colon, or ovary, presumably representing a cancer family syndrome (Lynch syndrome II). CONCLUSION: Our preliminary data not only show familial and probably heritable tendencies for endometrial adenocarcinoma, but further suggest that there are at least two distinct forms: (1) the previously described Lynch syndrome II (cancer family syndrome), and (2) a heretofore unemphasized entity characterized by a tendency to endometrial adenocarcinoma alone.

Adenocarcinoma↗
PubMed1992

Early sonographic evaluation for fetal growth delay and congenital malformations in pregnancies complicated by insulin-requiring diabetes. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study.

OBJECTIVE: It has been reported that early fetal growth retardation may be a useful marker for congenital malformations in diabetic pregnancies. To test this hypothesis, diabetic and nondiabetic women were sonographically evaluated during the first trimester. RESEARCH DESIGN AND METHODS: Fetal crown-rump lengths were measured sonographically at least once during the first 15 wk of pregnancy in 329 nondiabetic and 312 diabetic women. Of these, 289 nondiabetic and 269 diabetic women had sonograms before 10 wk of gestation and 283 nondiabetic and 269 diabetic women had sonograms between 10 and 15 wk of gestation. Early fetal growth delay was defined as a sonographic gestational age of greater than or equal to 6 days less than menstrual gestational age. RESULTS: The mean crown-rump lengths at 8 wk were 17.9 +/- 4.6 mm in the diabetic and 18.7 +/- 4.9 mm in the nondiabetic groups (P = 0.13). At 12 wk, the mean fetal crown-rump length was 58.5 +/- 8.8 mm for diabetic subjects and 60.6 +/- 8.7 mm for nondiabetic subjects (P = 0.04). Between 5 and 9 wk, 28 of 289 (9.7%) fetuses of nondiabetic subjects, 34 of 259 (13.1%) normal fetuses of diabetic subjects, and 2 of 10 (20%) malformed fetuses of diabetic subjects demonstrated growth delay (P = 0.31, normal vs. malformed diabetic). Between 10 and 15 wk of gestation, 28 of 283 (9.9%) fetuses of nondiabetic subjects, 32 of 256 (12.5%) normal fetuses of diabetic subjects, and 4 of 13 (30.8%) malformed fetuses of diabetic subjects demonstrated growth delay (P = 0.06, normal vs. malformed diabetic). Early fetal growth delay did not predict a reduced birth weight at term. CONCLUSIONS: Among insulin-dependent diabetic subjects who were moderately well controlled at conception, statistically significant but mild early fetal growth delay was present but did not appear to be useful clinically in predicting congenital malformations. Recommendations that growth delay demonstrated on early ultrasound be used as a predictor of congenital malformation require careful reexamination.

Adult↗
PubMed1992

Maternal serum screening for fetal Down syndrome in women less than 35 years of age using alpha-fetoprotein, hCG, and unconjugated estriol: a prospective 2-year study.

OBJECTIVE: To evaluate prospectively maternal serum screening with alpha-fetoprotein (AFP), hCG, and unconjugated estriol (uE3) as a screen for fetal Down syndrome. METHODS: Women less than 35 years of age were offered screening between 15-20 weeks' gestation. Screening results calculated by an algorithm to be equal to or greater than 1:274 (the risk of a 35-year-old for fetal Down syndrome at the second trimester) were considered positive. If gestational age was confirmed by ultrasonography, genetic counseling and amniocentesis were offered. RESULTS: In the first 2 years of our program, 9530 women were screened, of which 686 (7.2%) were found to be screen-positive. Ultrasonographic examination explained the abnormal values in 379 (4.0%). The remaining 307 (3.2%) received genetic counseling and 214 (2.2%) elected amniocentesis or CVS. Four cases of fetal Down syndrome and one de novo chromosomal marker were detected. In three additional cases of fetal Down syndrome, triple-analyte screening failed to identify the pregnancies to be at increased risk. None of the seven cases of fetal Down syndrome would have been detected through screening with maternal serum alpha-fetoprotein (MSAFP) and age alone. CONCLUSIONS: Measurement of MSAFP, hCG, and uE3 in women less than 35 years old is an effective screening test for fetal Down syndrome, with a sensitivity of 57% in our study and an amniocentesis rate (false-positive rate) of 3.2%.

Adult↗
PubMed1992

Preimplantation genetics and recovery of fetal cells from maternal blood.

Advances in molecular genetics have made possible advances in two new areas of prenatal diagnosis. Preimplantation genetic diagnosis is being explored through polar body biopsy, biopsy of the single cell from the eight-cell embryo, and trophectoderm biopsy of the blastocyst. There are attractive theoretical advantages to the last approach. However, assessment of pregnancies to be continued has been attempted only in the former two, and has succeeded only in the eight-cell embryo. A major problem with polar body biopsy is recombination for loci near the centromere, which may make analysis of the first polar body alone uninformative. DNA amplification of a single cell by polymerase chain reaction also has inherent pitfalls. Fetal cells in maternal circulation have ostensibly been shown to exist: lymphocytes, trophoblasts, and erythroblasts. The basis for this claim is polymerase chain reaction amplification showing fetal DNA sequences in maternal blood. Diagnosis of fetal chromosomal abnormalities requires techniques other than polymerase chain reaction, namely fluorescence in situ hybridization. Fetal trisomy has thus been detected by flow-sorting maternal blood for fetal erythroblasts followed by subjecting sorted cells to fluorescence in situ hybridization for chromosome-specific probes.

Animals↗