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R J Wapner

Publications and source records attributed to R J Wapner.

At least 37 records · Page 2Linked to original sources
PubMed1999

Selective termination for structural, chromosomal, and mendelian anomalies: international experience.

OBJECTIVE: Our purpose was to evaluate the outcomes of selective termination for fetal anomalies at 8 centers with the largest known experiences worldwide. STUDY DESIGN: Outcomes in 402 cases of selective termination in pregnancies with dizygotic twins from 8 centers in 4 countries were analyzed by year, gestational age at procedure, and indication. Reductions of fetuses were as follows: 2 to 1, n = 345; 3 to 2, 39; >/=4 to 2 or 3, n = 18. Potassium chloride was used in all procedures. RESULTS: Selective termination resulted in delivery of a viable infant or infants in >90% of cases. Loss up to 24 weeks occurred in 7.1% of cases in which the final result was a singleton fetus and in 13.0% of cases in which the final result was twins. Loss was 6.6% as a result of structural abnormalities, 7.0% for chromosomal abnormalities, and 10% for mendelian abnormalities (difference not statistically significant). Loss rates for procedures were as follows: 9-12 weeks, 5.4%; 13-18 weeks, 8.7%; 19-24 weeks, 6.8%; and >/=25 weeks, 9.1% (difference not statistically significant). Mean gestational age at delivery was 35.7 weeks. No differences were seen in outcomes by maternal age. The rate of very early premature deliveries has fallen in recent years. There were no known cases of disseminated intravascular coagulation or serious maternal complications. CONCLUSION: (1) Selective termination, in the most experienced hands, can be technically performed in all 3 trimesters with good outcomes in >90% of cases. (2) The previously observed increase in second- versus first-trimester losses has diminished. (3) Third-trimester procedures, where legal, can be performed with a good outcome for the surviving fetus.

Chromosome Aberrations↗
PubMed1999

Fetal cell identifiers: results of microscope slide-based immunocytochemical studies as a function of gestational age and abnormality.

OBJECTIVE: We evaluated monoclonal antibodies to 3 cell surface and 3 intracellular antigens for their relative usefulness as markers to identify fetal cells in maternal blood. STUDY DESIGN: With indirect immunocytochemical labeling techniques, antigen expression was studied in 52 fetal blood samples as a function of gestational age, fetal karyotype, the presence of multiple anomalies detectable on ultrasonography, and anemia. RESULTS: A decline in the expression of these antigens as gestational age advanced was demonstrated. Samples from karyotypically abnormal fetuses, fetuses with multiple anomalies, and anemic fetuses showed an antigenic distribution that was immature for gestational age. In normal fetuses zeta globin and epsilon globin expression decreased after 12 to 14 weeks, potentially limiting the utility of these proteins as fetal cell markers in the isolation of fetal cells from maternal blood. CONCLUSIONS: The results of this study demonstrate a fetal developmental hematologic profile that varies with gestational age and also with pathologic condition. Antibodies to the gamma chain of fetal hemoglobin and the transferrin receptor (CD71) are the most useful fetal cell-identifying reagents.

Abnormalities, Multiple↗
PubMed1999

First trimester prenatal diagnosis: chorionic villus sampling.

Chorionic villus sampling has been used successfully for first trimester diagnosis of genetic disorders for over 14 years. When performed between 10 and 14 weeks' gestation, it is both safe and effective in the diagnosis of fetal chromosomal, biochemical, and molecular disorders, with risks comparable to those of second trimester amniocentesis. Cytogenetic results have been confirmed to be reliable and accurate. Although confined placental mosaicism occurs in approximately 1% of cases requiring interpretation, and occasionally additional invasive testing, its finding adds additional information about perinatal outcome and can alert the practitioner to fetal genetic disorders. Earlier concerns about procedure-induced limb defects have been reduced with the accumulation of additional data, showing minimal to no risk when chorionic villus sampling is performed after 70 days of gestation. In experienced hands, it may be the procedure of choice for sampling multiple gestations. Secondary to the advantage of safe, early diagnosis, chorionic villus sampling appears to be the optimal choice for first trimester testing.

Abortion, Spontaneous↗
PubMed1999

International, collaborative assessment of 146,000 prenatal karyotypes: expected limitations if only chromosome-specific probes and fluorescent in-situ hybridization are used.

The development of chromosome-specific probes (CSP) and fluorescent in-situ hybridization (FISH) has allowed for very rapid identification of selected numerical abnormalities. We attempt here to determine, in principle, what percentage of abnormalities would be detectable if only CSP-FISH were performed without karyotype for prenatal diagnosis. A total of 146 128 consecutive karyotypes for prenatal diagnosis from eight centres in four countries for 5 years were compared with predicted detection if probes for chromosomes 13, 18, 21, X and Y were used, and assuming 100% detection efficiency. A total of 4163 abnormalities (2.85%) were found including 2889 (69. 4%) (trisomy 21, trisomy 18, trisomy 13, numerical sex chromosome abnormalities, and triploidies) which were considered detectable by FISH. Of these, 1274 were mosaics, translocations, deletions, inversions, rings, and markers which would not be considered detectable. CSP-FISH is a useful adjunct to karyotype for high risk situations, and may be appropriate in low risk screening, but should not be seen as a replacement for karyotype as too many structural chromosome abnormalities will be missed.

Chromosome Aberrations↗
PubMed1998

Long-term magnesium sulfate tocolysis and maternal osteoporosis in a triplet pregnancy: a case report.

Prolonged infusion of magnesium sulfate has been used for the treatment of refractory preterm labor. Long-term magnesium sulfate tocolytic therapy either alone or in combination with other tocolytic agents has been reported to be safe and effective with minimal maternal side effects. There has been only one previous report of a disturbance in maternal calcium homeostasis, which included decreased distal radius bone density and hypercalciuria as a result of prolonged magnesium sulfate infusion. This article reports the first case of bilateral fracture of the calcanei in the postpartum period secondary to osteoporosis associated with prolonged magnesium sulfate tocolysis and bed rest. A 35-year-old white female with a triplet pregnancy of 25 weeks' gestation was admitted in preterm labor. Bed rest, intravenous magnesium sulfate tocolysis, and intermittent subcutaneous terbutaline were necessary to maintain uterine quiescence for 65 days. The patient received weekly betamethasone for 6 weeks for the acceleration of fetal lung maturation. Daily prenatal multivitamins and low-dose subcutaneous heparin for thromboprophylaxis were given. Efforts at tocolysis were ultimately not successful and the patient underwent a cesarean section delivery at 34 2/7 weeks' gestation. The patient's postoperative course was complicated by osteoporosis and bilateral stress fractures of the calcanei. This case report demonstrates that stress fractures secondary to osteoporosis may be associated with prolonged magnesium sulfate therapy and bed rest in higher order multiple pregnancy. Other possible contributing factors to osteoporosis include heparin thromboprophylaxis and suboptimal calcium supplementation. Therefore, in circumstances of prolonged bed rest and magnesium sulfate tocolysis, additional daily calcium supplementation would be well advised.

Adult↗
PubMed1998

Prenatal confirmation of true fetal trisomy 22 mosaicism by fetal skin biopsy following normal fetal blood sampling.

Trisomy 22 mosaicism diagnosed at 20 weeks' gestation by amniocentesis in a 35-year-old woman was not confirmed by fetal blood sampling. Subsequent fetal skin biopsy revealed trisomy 22 in 7 of the 15 fibroblasts analysed. We conclude that, depending on the chromosome involved, fetal skin biopsy should be considered in the diagnostic work-up when mosaicism is found in amniotic fluid.

Abortion, Induced↗
PubMed1998

Human ejaculate. Effects on the biomechanical properties of the human chorioamniotic membranes.

OBJECTIVE: To determine the effects of human ejaculate on the biomechanical properties of the human chorioamniotic membranes. STUDY DESIGN: Equivalent strips of chorioamniotic membranes were obtained from 30 term, uncomplicated pregnancies immediately after delivery and incubated for 0, 1 and 24 hours with either ejaculate or pseudoamniotic fluid. Three biomechanical properties--rupture tension, strain to rupture and work to rupture--were compared. RESULTS: One hour of incubation with pseudoamniotic fluid alone did not significantly change the membrane biomechanical parameters, but these parameters were reduced after one hour of exposure to ejaculate (P < .05). Twenty-four hours of incubation decreased all three properties in both the ejaculate and control groups without any significant difference between the two groups. CONCLUSION: In vitro exposure to human ejaculate for one hour significantly weakens the human chorioamniotic membranes.

Amnion↗
PubMed1998

Efficacy of fibrin glue for in vitro sealing of human chorioamniotic membranes.

OBJECTIVE: To assess the changes in tensile strength properties of artificially punctured chorioamniotic membranes after sealing the defect with fibrin glue, a tissue sealant. STUDY DESIGN: Chorioamniotic membranes were obtained from 30 term, uncomplicated pregnancies immediately after delivery. Adjacent, same-sized strips were cut from each membrane sample. After baseline tensile strength properties were obtained, identical size holes were made on each strip, and fibrin glue was applied onto half the specimens. Following adequate stabilization of fibrin, tensile strength properties--rupture tension, strain to rupture and work to rupture--were measured. RESULTS: Membrane puncture decreased the tensile strength characteristics, indicating weakening of the chorioamniotic membranes: Rupture tension (g/cm) dropped from 153.1 +/- 12.3 to 76.8 +/- 15.7; strain to rupture (%) from 193.9 +/- 29.9 to 152.6 +/- 36.8; and work to rupture (g x cm) from 560.8 +/- 51.8 to 239.0 +/- 65.5 (P < .05). Significant increases were noted in rupture tension (116.0 +/- 19.6), strain to rupture (173.5 +/- 30.8) and work to rupture (394.3 +/- 91.3) after application of fibrin glue; however, all three measurements remained less than prepuncture values (P < .05). CONCLUSION: Fibrin glue effectively improved the structural integrity of artificially punctured chorioamniotic membranes.

Amnion↗
PubMed1997

Search for the optimal fetal cell antibody: results of immunophenotyping studies using flow cytometry.

Fetal nucleated cells circulating in maternal peripheral blood are a noninvasive source of fetal DNA for prenatal genetic diagnoses. The successful isolation of fetal cells from maternal blood depends upon identification of differences between fetal and maternal cell surface antigen expression. To our best knowledge, a monoclonal antibody that binds only fetal blood cells has not yet been identified. We studied antigens recognized by six different monoclonal antibodies for their biologic expression on fetal blood cells as a function of gestational age, and compared their ability to bind fetal but not maternal cells. The results suggest a relationship between gestational age and nucleated cell surface antigen expression. The monoclonal antibodies FB3-2, H3-3, CD71 and 2-6B/6 are suitable reagents for first or early second trimester fetal cell isolation, although FB3-2 and H3-3 are more specific for fetal cells due to significantly lower expression of these antigens on maternal mononuclear cells. The observation that samples from fetuses with chromosome abnormalities or multiple structural anomalies express higher levels of these antigens indicates that these reagents will potentiate the detection of abnormal fetal cells in maternal blood samples.

Abnormalities, Multiple↗
PubMed1997

Cervical ultrasonography compared with manual examination as a predictor of preterm delivery.

OBJECTIVE: Our purpose was to compare the accuracy of ultrasonographic and manual cervical examinations for the prediction of preterm delivery. STUDY DESIGN: One hundred two singleton pregnancies at high risk for preterm delivery were followed up prospectively from 14 to 30 weeks with both serial cervical ultrasonography measurements and manual examinations of the length of the cervix. The primary outcome studied was preterm (< 35 weeks) delivery. RESULTS: Excluding six induced preterm deliveries, 96 pregnancies were analyzed. The mean cervical length measured by ultrasonography was 20.6 mm in pregnancies delivered preterm (n = 17) and 31.3 mm in pregnancies delivered at term (n = 79) (p = 0.003); the mean cervical lengths measured by manual examination were 16.1 mm and 18.6 mm in the same preterm and term pregnancies, respectively (not significant). The sixteenth- and twentieth-week ultrasonographic cervical lengths predicted preterm delivery most accurately (p < 0.0005). The 25th percentiles of ultrasonographic (25 mm) and manual (16 mm) cervical lengths showed relative risks for preterm delivery of 4.8 (95% confidence interval 2.1 to 11.1, p = 0.0004) and 2.0 (95% confidence interval 0.5 to 4.7, p = 0.1), respectively; sensitivity, specificity, and positive and negative predictive values were 59%, 85%, 45%, 91%, and 41%, 77%, 28%, and 86%, respectively. CONCLUSION: Cervical length measured by ultrasonography is a better predictor of preterm delivery than is cervical length measured by manual examination. Cervical ultrasonography in patients at high risk for preterm birth seems to be most predictive of preterm delivery when it is performed between 14 and 22 weeks' gestation.

Cervix Uteri↗
PubMed1997

Chorionic villus sampling.

Chorionic villus sampling (CVS) has been used a successful and safe first-trimester prenatal diagnostic technique for over 12 years. Developed to avoid the medical and psychological complications of later prenatal diagnosis by amniocentesis, CVS rapidly has become a primary tool for the diagnosis of fetal cytogenetic, molecular, and biochemical disorders. In addition, its development has led to an improved understanding of several biological processes, including confined placental mosaicism and uniparental disomy.

Chorionic Villi Sampling↗
PubMed1997

Cervical funneling: sonographic criteria predictive of preterm delivery.

Our objective was to establish sonographic criteria that are predictive of preterm delivery in patients with internal os dilatation (funneling). The study population consisted of patients with cervical funneling identified on translabial or transvaginal ultrasound examination. Funnel length, functional length, percentage funneling and funnel width were evaluated for their predictive values for preterm delivery. In the 43 patients who met the study criteria, funneling was detected at a mean gestational age of 21.4 weeks (range 16-28). Twenty-three of 31 patients (74%), manually examined immediately following the ultrasound examination, had a closed cervix. Preterm delivery occurred in 42% of patients. Funnel length of > or = 16 mm, functional length of < or = 20 mm, funneling of > or = 40% and funnel width of > or = 14 mm correlated significantly with preterm delivery. Patients with funneling of < 25%, 25-50% and > 50% had preterm delivery rates of 17%, 29% and 79%, respectively.

Adult↗
PubMed1997

First-trimester growth patterns of aneuploid fetuses.

First-trimester growth restriction has been reported in certain aneuploid pregnancies. The purpose of this study was to evaluate this association further by comparing the crown-rump lengths (CRLs) and growth rates from 196 chromosomally abnormal fetuses with a control population of 1929 euploid fetuses. The mean CRLs and growth rates were significantly reduced (P < 0.05) in the groups of fetuses with trisomy 18 (n = 49), trisomy 13 (n = 19), and triploidy (n = 8). Using a fifth percentile cut-off, growth rate was a better discriminator than a single CRL in identifying fetuses affected with these aneuploidies. These growth parameters were not significantly reduced in fetuses with trisomy 21 (n = 92), sex chromosome trisomies (n = 20), or 45,X (n = 8). We conclude that fetal growth restriction associated with an underlying chromosome abnormality can occur as early as the first trimester. This phenomenon results from intrinsic fetal factors and not delayed ovulation. Such information is important to establish as first-trimester serum screening evolves.

Aneuploidy↗
PubMed1997

Mosaicism: implications for postnatal outcome.

Mosaicism detected in the cytogenetic analysis of chorionic villi or cultured amniocytes can present a difficult and at times impossible interpretative dilemma. The finding may be indicative of a generalized fetal mosaicism. However, in the majority of cases, the abnormal cell line is representative of either an in-vitro event or a chromosomal error that is restricted to the extra-embryonic tissues. Advances in laboratory medicine have provided insight into the determination of which cases of true mosaicism have the greatest risk of being clinically significant with regard to the fetal genotype and phenotype. Despite the presence of a normal fetal karyotype, certain chromosomes involved in confined placental mosaiciam may increase the risk of poor perinatal outcome or predispose the fetus or neonate to the adverse effects of genetic imprinting owing to the development of uniparental disomy.

Amniocentesis↗
PubMed1996

Prolongation of pregnancy and survival of remaining fetuses after operative evacuation of one triplet at 18 weeks' gestation.

BACKGROUND: Successful delay of aftercoming siblings is an infrequent event in obstetrics. No case of second-trimester operative vaginal evacuation of a fetus followed by delayed delivery of the remaining siblings has been described previously. CASE: A triplet pregnancy was complicated by preterm rupture of membranes at 17 weeks' gestation, followed by cord prolapse and subsequent fetal arm prolapse at 18 weeks' gestation. Operative evacuation of triplet A was performed under ultrasound guidance, with the placenta left undisturbed. Antibiotics and tocolytics were used perioperatively and the pregnancy was prolonged for another 16 weeks. Onset of active labor at 34 weeks' gestation resulted in the vaginal delivery of viable twin males weighing 2810 and 2680 g. CONCLUSION: In cases of multiple gestations with second-trimester rupture of the lower sac, selective fetal evacuation can be performed safely and may allow successful continuation of the remaining pregnancy.

Adult↗
PubMed1996

Multifetal pregnancy reduction: evaluation of fetal growth in the remaining twins.

OBJECTIVE: Our purpose was to study fetal growth after reduction of high-order multiple gestations to twins. STUDY DESIGN: Birth weight and gestational age data were collected for 236 triplet and greater multiple pregnancies reduced to twins (113 triplets, 89 quadruplets, and 34 quintuplets or above) and was compared with those of a control group of unreduced twins. RESULTS: Rates of intrauterine growth restriction per pregnancy were significantly different between the nonreduced and all categories of reduced multifetal pregnancies. The incidence of intrauterine growth restriction was 19.4% in the nonreduced twins, 36.3% in pregnancies reduced from triplets, 41.6% in pregnancies reduced from quadruplets, and 50% from higher-order multiple gestations. There was a statistically significant trend toward increasing frequency of intrauterine growth restriction with increasing starting fetal number (p = 0.04). The increase in intrauterine growth restriction was primarily accounted for by twin pairs with only one growth-restricted newborn. CONCLUSION: Multifetal pregnancy reduction does not reduce the incidence of intrauterine growth restriction in the remaining fetuses to that of nonreduced twins.

Birth Weight↗
PubMed1996

Prenatal diagnosis using fetal cells isolated from maternal peripheral blood: a review.

Many questions remain about the feasibility of using fetal cells from maternal blood for prenatal diagnosis. Although recently there has been more focus on clinically relevant methods, many studies have been performed using blood drawn after invasive procedures, and over a wide range of gestational ages. For methods to be applicable to clinical use, more work is needed on isolating cells early in pregnancy, when termination is still an option for parents who are found to have an affected pregnancy. It is generally agreed that fetal nucleated erythrocytes are the most efficacious cell type for prenatal diagnosis, but it has not yet been shown definitively whether there is an ideal gestational age for sampling, whether ABO incompatibility might limit availability of fetal cells, or whether the number of cells present might be different in normal versus abnormal pregnancies. PCR has been shown to be a powerful tool in allowing amplification and identification of very small amounts of fetal DNA. However, this is limited to cases in which a specific and unique gene from the father is sought. This means that there is the potential to diagnose many paternally inherited autosomal dominant diseases and some autosomal recessive diseases, in which the parents have different and identifiable mutations. However, when parents are both carriers of the same autosomal recessive mutations, or when the disease is X linked, PCR will not aid in prenatal diagnosis. Cytogenetic analysis of fetal cells by FISH after cell sorting is another potentially useful method of prenatal diagnosis, but requires relatively pure samples of fetal cells or an independent marker that allows easy microscopic identification. The latter might be accomplished by identifying fetal cells through their expression of embryonic hemoglobins or because they contain HLA-G mRNA. In addition, current techniques of cell sorting must be improved so that a higher percentage of fetal cells can be isolated. Currently, the best cell sorting techniques usually produce a maximum purity of 10% fetal cells. Commonly, in normal pregnancies, fewer than 0.1% of the cells isolated after sorting are fetal in origin. Improving the concentration and quantity of fetal cells will improve the accuracy of FISH. Methods such as immunophenotyping that allow the selective identification of fetal cells by microscopy, and can be used in conjunction with FISH, may be extremely valuable because they may allow the genetic analysis of only the few fetal cells within a background preponderance of maternal cells. Although the retrieval of fetal cells from maternal blood is an attractive concept, it must be clearly stated that presently it is only in the investigational phase because of the low sensitivity and specificity. There is no current application for these methods in clinical practice. It remains to be determined whether testing maternal blood for fetal cells or DNA will be used as a screening tool, similar to the maternal serum screening currently in use, or whether the accuracy can be improved to a level such that the techniques can be used diagnostically. Although there are many questions that remain unanswered at this time, the outlook for noninvasive prenatal genetic testing in the future is optimistic.

Erythrocytes↗