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Biomedical subjects

J L Simpson

Publications and source records attributed to J L Simpson.

At least 127 records · Page 7Linked to original sources
PubMed1991

Vitamins, folic acid and neural tube defects: comments on investigations in the United States.

No clear answer concerning whether multivitamin/folate supplementation prevents neural tube defects (NTDs) is provided by three studies in the United States. All these studies are occurrence in nature, no recurrence studies having been conducted. The Atlanta Birth Defects Study is subject to pronounced memory and recall biases, the length between event and interview being as long as 16 years. In a second study (Boston University), objections can be raised to certain aspects of the experimental design, and the claim that 22 per cent of women started vitamins sufficiently early after pregnancy diagnosis to influence NTD formation is suspicious. Our NICHD case control study of 541 women in California and Illinois revealed no evidence for multivitamins or folic acid preventing NTDs. U.S. public policy-makers face difficulties in applying results of recurrence or occurrence studies in high-risk areas to low-risk areas in the U.S.

Female↗
PubMed1991

Alpha-fetoprotein and acetylcholinesterase are not predictive of fetal junctional epidermolysis bullosa, Herlitz variant.

Junctional epidermolysis bullosa, Herlitz variant (junctional EB-Herlitz) is a lethal autosomal recessive skin disorder currently amenable to prenatal diagnosis only by direct analysis of fetal skin. However, elevated levels of alpha-fetoprotein, as well as the presence of acetylcholinesterase in amniotic fluid, have been associated with other severe fetal genodermatoses. Fetal skin samplings were performed in ten pregnancies at risk for fetal junctional EB-Herlitz, with three fetuses affected on the basis of electron microscopic detection of blisters within the lamina lucida and abnormal hemidesmosomes. In neither affected nor unaffected pregnancies were maternal serum or amniotic fluid alpha-fetoprotein levels elevated. Moreover, alpha-fetoprotein levels in both maternal serum and amniotic fluid were not statistically different comparing affected and unaffected fetuses. Acetylcholinesterase was not present in the amniotic fluid samples of the three affected pregnancies. Unlike other severe fetal genodermatoses, neither alpha-fetoprotein nor acetylcholinesterase was predictive of junctional EB-Herlitz.

Acetylcholinesterase↗
PubMed1991

Sister chromatid exchange (SCE) frequencies differ between directly prepared cytotrophoblasts and cultured mesenchymal core cells.

Analysis of sister chromatid exchange (SCE) in chorionic villus cells may become useful in measuring the response of fetal tissues to clastogens or mutagens or for prenatal diagnosis of chromosome breakage syndromes such as Bloom syndrome. Previous studies have failed to analyze cytotrophoblastic cells and mesenchymal core cells, or have found no difference between SCE frequencies in directly prepared and cultured cells. Our data indicate significant differences in SCE frequencies between the two cell types: SCE frequency in directly prepared cytotrophoblasts was 6.73 SCE/cell +/- 1.6, whereas SCE frequency in cultured mesenchymal core cells was 10.31 SCE/cell +/- 0.49 (P less than 0.001). SCE analyses involving chorionic villi must take into account cell type.

Animals↗
PubMed1991

Sister chromatid exchange frequency in directly prepared cytotrophoblasts: demonstration of in vivo deoxyribonucleic acid damage in pregnant women who smoke cigarettes.

Assessing frequency of sister chromatid exchange is a sensitive method of monitoring exposure to clastogens, mutagens, and other substances that induce deoxyribonucleic acid damage. Aware that cigarette smoke is associated with increased sister chromatid exchange in many cell types, we sought to determine whether an in vivo effect of cigarette smoke could be demonstrated by study of sister chromatid exchange in chorionic villus cells. Directly prepared cytotrophoblasts and cultured mesenchymal core cells were analyzed. Mean sister chromatid exchange frequency in cytotrophoblasts from smoking subjects (8.87 sister chromatid exchanges per cell) was significantly greater than in nonsmoking subjects (5.81 sister chromatid exchanges per cell; p less than 0.001); however, no significant difference in cultured mesenchymal core cells was found. Our results demonstrate that maternal exposure to cigarette smoke results in direct placental deoxyribonucleic damage, which in turn could explain deleterious effects of smoking on pregnancy. Increased sister chromatid exchange frequency was observed only in directly prepared cytotrophoblasts, showing the necessity of using this cell type to evaluate the effects of clastogens on placentas.

Chorionic Villi↗
PubMed1991

Does unexplained second-trimester (15 to 20 weeks' gestation) maternal serum alpha-fetoprotein elevation presage adverse perinatal outcome? Pitfalls and preliminary studies with late second- and third-trimester maternal serum alpha-fetoprotein.

Several reports have suggested that persons with an unexplained maternal serum alpha-fetoprotein elevation at 15 to 20 weeks' gestation are at an increased risk for a variety of other pregnancy complications (e.g., preeclampsia) and adverse perinatal outcomes (e.g., fetal death, low-birth-weight infants). However, ascertainment biases could explain some of these reported findings, and predictive value of unexplained elevated maternal serum alpha-fetoprotein levels in the prediction of pregnancy complications seems limited. If elevated second-trimester levels were truly predictive of pregnancy complications, we reason that third-trimester levels could prove even more useful. We thus studied late second-trimester and early third-trimester (24 to 36 weeks' gestation) maternal serum alpha-fetoprotein levels with the same enzyme immunoassay we use to evaluate routine second-trimester (15 to 20 weeks' gestation) levels. Values rose up to 32 weeks and fell slightly thereafter. Variance was greater than at 15 to 20 weeks but not so great as to preclude clinical usefulness in the third trimester. Of 279 women with a normal (0.4 to 2.49 multiples of the median) maternal serum alpha-fetoprotein value at 15 to 20 weeks' gestation, 270 (96.8%) showed levels in the same range later in gestation; however, none of six singleton pregnancies with unexplained maternal serum alpha-fetoprotein levels greater than 2.50 multiples of the median at 15 to 20 weeks' gestation showed maternal serum alpha-fetoprotein levels in this range at 24 to 36 weeks' gestation. The relationship between second- and third-trimester maternal serum alpha-fetoprotein levels in abnormal pregnancies remains to be elucidated in a large sample. Thus we are conducting not only cohort but also cross-sectional studies. Preliminary findings suggest that women with preterm premature rupture of membranes or with premature labor show elevated late second-trimester and early third-trimester maternal serum alpha-fetoprotein levels; however, larger sample sizes are necessary.

Female↗
PubMed1991

Carrier screening for cystic fibrosis: implications for obstetric and gynecologic practice.

Cystic fibrosis, which is one of the most common autosomal recessive disorders, has a carrier frequency of approximately 1 in 25 among whites in the United States. In this population approximately 75% of the mutations in patients with cystic fibrosis correspond to a 3 base pair deletion that results in the loss of a phenylalanine residue at amino acid position 508 (designated delta F508) from the coding region of the cystic fibrosis gene. Currently, only about half of the couples at risk can be identified as cystic fibrosis carriers. We support conclusions of the National Institutes of Health Workshop on Population Screening for the Cystic Fibrosis Gene, which state that carrier testing should be offered to all individuals or couples with a family history of cystic fibrosis. Good science and solid educational and counseling strategies must be in place before screening for cystic fibrosis is routinely offered to those with a negative family history. Pilot programs that investigate research questions in the delivery of population screening for cystic fibrosis carriers are urgently needed.

Advisory Committees↗
PubMed1991

Fetal outcome among pregnancies in natural family planning acceptors: an international cohort study.

This international, multicenter, prospective cohort study examines the outcome of pregnancies associated with aging gametes. Comparing pregnancies conceived at or near the peak mucus phase with those occurring before or after the peak provides a means of evaluating the effect of aging gametes. The outcome criteria are (1) rates of spontaneous abortion, (2) low birth weight, and (3) congenital malformations. Preliminary analysis shows a trend toward increased spontaneous abortion with aging gametes in certain subsets (women with prior pregnancy losses) but no effect on birth weight. Too few method failures have yet been studied to make a definitive statement on congenital malformations.

Family Planning Services↗
PubMed1991

Segregation analysis and genetic counseling when both parents carry balanced chromosomal translocations.

OBJECTIVE: To assess the risk of chromosomally abnormal offspring and discuss counseling approach when both parents carry balanced translocations. DESIGN: Theoretical segregation analysis is performed and use of empiric data is used in genetic counseling. SETTING: Patients are referred to Division of Reproductive Genetics at the University of Tennessee, Memphis. PATIENTS, PARTICIPANTS: The mother, heterozygous for reciprocal translocation 46,XX, rcp(7;13)(p21;q22) and father, heterozygous for Robertsonian translocation 45,XY,rob(13q;14q) were referred for genetic counseling concerning risks of chromosomally abnormal offspring. INTERVENTIONS: Segregation analysis, genetic counseling, and chorionic villus sampling. MAIN OUTCOME MEASURE(S): A cumulative risk was derived to use for counseling purposes. Cytogenetics using GTG-banding was performed on cultured chorionic villus cells. RESULTS: Theoretical risk of this couple having chromosomally abnormal offspring was 40.5%. On the basis of empirical data and risk factors inherent in the specific translocations, the maternal contribution at midtrimester was 3.5%; the paternal contribution was 1% to 2%. The sum of these risks was used in counseling. CONCLUSIONS: The fetus was found to be 46,XY,rcp(7;13)(p21;q22).

Abortion, Habitual↗
PubMed1991

Screening for fetal and genetic abnormalities.

Screening for genetic abnormalities is an integral part of obstetrics. Prior to initiating screening, however, several prerequisites must be met: (i) capacity to alter clinical management, (ii) cost effectiveness, (iii) reliable means (usually assays) of assessment, and (iv) capacity to handle problems. In all pregnancies one should determine in systematic fashion whether family history places a pregnant woman at increased risk over the background risk of 2-3% congenital anomalies. All women over age 35 years at delivery should be offered prenatal cytogenetic testing, and women of all ages should be offered maternal serum alpha-fetoprotein screening for neural tube defects. Screening ostensibly normal populations is appropriate in certain ethnic groups to determine heterozygosity for selected disorders: Blacks for sickle-cell anaemia, Mediterranean people for beta-thalassaemia, Southeast Asians and Filipinos for alpha-thalassaemia, Ashkenazi Jews and perhaps French-Canadians for Tay-Sachs disease. Cystic fibrosis screening (delta F508 mutations) is not currently recommended for the general populations, but should be offered to relatives of an individual having delta F508 cystic fibrosis. Irrespective of the extent of screening programmes for Mendelian traits, the mutant allele will remain in the general population because by far the greatest genetic load lies in clinically normal heterozygotes, affected contributing far less to the load despite the obvious clinical effect.

Abortion, Legal↗
PubMed1991

Fetal cells in the maternal circulation: isolation by multiparameter flow cytometry and confirmation by polymerase chain reaction.

During pregnancy, nucleated fetal erythrocytes enter the maternal circulation and can be isolated efficiently from the maternal cells by multiparameter flow cytometry. Male DNA, implying presence of a male fetus, can be identified in flow-sorted maternal blood by polymerase chain reaction with oligonucleotide primers flanking single-copy Y-specific DNA sequences. Among flow-sorted samples, we correctly identified fetal sex in 17/18 (94%) pregnancies of 10-21 weeks gestation. Maternal blood thus provides a potential opportunity for prenatal diagnosis that could preclude the need for invasive procedures in current use.

Base Sequence↗
PubMed1991

Genetic heterogeneity in neural tube defects.

In 1985-1987, the authors attempted to ascertain all cases of confirmed neural tube defects (NTD) in California and Illinois, not only among live-born infants (postnatal) but also cases ascertained during pregnancy (prenatal). Mothers of both prenatal and postnatal NTD cases were interviewed within 5 months. Among postnatal NTD cases, 14.9% (45/303) had anomalies not ordinarily associated with NTD. The frequency of non-NTD related anomalies was 9.4% (5/53) in anencephaly, 0/3 in craniorachischisis, 22.9% (8/35) in encephalocele, 14.5% (27/186) in spina bifida, 20% (1/5) in multiple NTD cases and 19% (4/21) in other NTDs. However, relatively few postnatal NTD cases had known multiple malformation patterns; Meckel-Gruber syndrome was the most common, with 2 postnatal cases, and 3 additional prenatal cases. Maternal age, paternal age and birth order in postnatal cases were 26.7 +/- 5.4 SD, 28.9 +/- 5.8 and 2.8 +/- 1.8, respectively. These characteristics were similar in prenatal NTD cases (27.9 +/- 6.0, 30.1 +/- 6.3, 2.5 +/- 1.5, respectively). We also found no differences in parental ages among different types of NTD. Frequency of prior spontaneous abortion differed neither between postnatal NTD (9.3%) and postnatal controls (8.1%), nor between prenatal NTD (10.7%) and prenatal control (8.7%). Loss rates in the pregnancy immediately prior to the index NTD cases were not significantly higher than in control subjects. The high frequency of non-NTD associated malformations (14.9%) indicates the caution must be exercised before assuming that a given NTD case is polygenic-multifactorial in etiology, especially cases of encephalocele.

Abnormalities, Multiple↗
PubMed1990

Risk of neural tube defects in relation to maternal fertility and fertility drug use.

In a case-control study to investigate whether women who use drugs to induce ovulation are at increased risk of conception of a child with a neural tube defect, 571 women who had a fetus or child with a neural tube defect, 546 women who had a fetus or child with other abnormalities, and 573 women who had an apparently normal fetus or child were questioned about infertility, fertility drug use, and related obstetric problems. The rate of maternal fertility drug use around the time of conception was not significantly higher for neural tube defects than for other abnormalities (odds ratio 1.28; 95% confidence interval 0.39, 4.51) or no abnormalities (odds ratio 0.80; 95% Cl 0.27, 2.27). Fertility drug use at any time was not significantly more frequent for neural tube defects than for other abnormalities (odds ratio 1.37; 95% Cl 0.70, 2.74) or no abnormalities (odds ratio 1.05; 95% Cl 0.56, 1.98).

Abnormalities, Drug-Induced↗
PubMed1990

Incidence and timing of pregnancy losses: relevance to evaluating safety of early prenatal diagnosis.

Knowing the frequency and timing of pregnancy loss during normal gestation is integral to evaluating the safety of prenatal diagnostic techniques. That preclinical loss rates are high in humans has long been suspected, but in the past decade new data concerning these losses have become available. Cohort studies indicate that many women who show positive beta-HCG assays never show clinical evidence of pregnancy. Cytogenetic abnormalities have also recently been documented in 20% of ostensibly normal in vitro fertilization embryos. All the above are consistent with the sentinel studies of Hertig and Rock, who showed high frequencies of morphological abnormalities in preimplantation embryos. The frequency of fetal losses after clinical recognition of pregnancy is 12-15%; however, more sensitive (ultrasonographic) methods of detecting fetal demise now indicate that most clinically recognized pregnancies occur prior to 8-9 weeks, being retained in utero 2-3 weeks prior to expulsion. Loss rates are influenced by maternal age, smoking, alcohol, and other confounding variables that if not taken into account could yield spurious results concerning safety of prenatal diagnostic techniques. After 8 weeks gestation the likelihood of losing a viable pregnancy is only 3% and after 16 weeks only 1%.

Abortion, Habitual↗
PubMed1990

Failure to document fetal cells in maternal circulation using the Selypes-Lorencz "air-culture" cytogenetic technique.

Isolating and analyzing fetal cells circulating in the maternal circulation would allow a relatively noninvasive method (i.e., venipuncture) for prenatal cytogenetic diagnosis. Several groups have claimed evidence for the presence of fetal cells in maternal circulation, and in one communication, Selypes and Lorencz (1988) reported the presence of relatively large numbers of fetal mitotic cells in phytohemagglutinin-stimulated blood cultures derived from pregnant women. We employed the laboratory method of Selypes and Lorencz in evaluating maternal blood from 29 patients (9.7 to 19.5 weeks gestation) in which the fetal complement differed from that of the mother (e.g., 46,XY, aneuploidy). Unfortunately, we were unable to confirm the results of Selypes and Lorencz.

Cell Separation↗