Microdeletions/duplications involving TBX1 gene in fetuses with conotruncal heart defects which are negative for 22q11.2 deletion on fluorescence in-situ hybridization.

OBJECTIVES: Conotruncal heart defects (CTD) are associated with del22q11.2 syndrome, which is often diagnosed by fluorescence in-situ hybridization (FISH). However, in those negative for del22q11.2 on FISH, the etiology is usually obscure. We aimed to use high-resolution array comparative genomic hybridization (array CGH) to clarify the underlying genetic causes in these cases. METHODS: In this retrospective study, fetal samples of amniocytes or fibroblasts, taken either for prenatal diagnosis by amniocentesis or for postnatal survey after termination of pregnancy, were obtained from 45 fetuses with CTD and were investigated by cytogenetic analysis including karyotyping and FISH for del22q11.2 syndrome. Eight fetuses with no findings on karyotyping and FISH were investigated further by array CGH, real-time quantitative polymerase chain reaction (qPCR) and Sanger sequencing of TBX1. RESULTS: Array CGH revealed that three of the eight fetuses carried submicroscopic genomic imbalances. Of these, two cases showed similar small microdeletions/duplications in 22q11.2 (one 0.85 kb microdeletion and one 8.51 kb microduplication). The minimal shared region spanned exon 2 of TBX1, a candidate gene responsible for cardiovascular defects in del22q11.2 syndrome. In all eight cases, the array CGH results were confirmed by qPCR, and Sanger sequencing did not detect other molecular pathologies. CONCLUSION: Our findings indicate an association between TBX1 variations and fetal CTD. The results also demonstrate the power of array CGH to further scrutinize the critical gene(s) of del22q11.2 syndrome responsible for heart defects. Array CGH apparently has diagnostic sensitivity superior to that of FISH in fetuses with CTD associated with del22q11.2 (and dup22q11.2) syndrome.

Delivery of the second twin.

OBJECTIVE: To determine the likelihood of cesarean for the second twin after vaginal delivery of the first and the risk of vaginal delivery. METHOD: A retrospective analysis of twin deliveries was performed on 10,365 live born twin pairs (20,730 births), using birth certificate data from the State of Illinois from 1997 through 2000. RESULT: The incidence of cesarean for the second twin after vaginal delivery of the first was 10.1%. The greatest incidence of failed vaginal delivery of the second twin was in the vertex/non-vertex group. Five-minute Apgar scores <4 were significantly more frequent in vaginally delivered twins <2000 g compared to those delivered via cesarean (p<0.001). CONCLUSION: Twin presentation type is predictive of the likelihood of a failed vaginal delivery of the second twin. Cesarean appears to significantly reduce the incidence of Apgars <4 for neonates <2000 g.

First-trimester trisomy screening: nuchal translucency measurement training and quality assurance to correct and unify technique.

OBJECTIVE: To describe the process of training for measuring nuchal translucency at five clinical centers in North America and to evaluate methods of quality assurance and feedback. DESIGN: Throughout a period of 18 months, the performance of sonographers in measuring fetal nuchal translucency was monitored using qualitative and quantitative methods of review. After 12 months, different approaches (written and personal feedback) were used to inform sonographers of technical aspects that needed to or could be improved. RESULTS: On initial qualitative review, discrepancies in judgment from different reviewers coincided with suboptimal magnification, failure to visualize the amniotic membrane and/or use of cross-shaped calipers. At subsequent global review, 13 (29%) images of nuchal translucency measurements were considered unacceptable. Quantitative assessment revealed that, during the first part of the study, the means from four sonographers were significantly smaller and the mean from the fifth sonographer was significantly larger than expected on the basis of findings from The Fetal Medicine Foundation (P < 0.0001). Following feedback, sonographers who underestimated nuchal translucency and who received a written report only did not change measurements overall (P = 0.9759). In contrast, those who received additional intervention showed a marked difference (P < 0.0001). CONCLUSIONS: Global qualitative review of images from one sonographer may be preferable to assessment of individual aspects of images. Results from global qualitative review correspond well with findings from quantitative analysis, indicating that the latter can be applied for ongoing audit. Observation of divergent results should prompt extensive personal feedback, rather than a written report, to prevent sonographers from settling in their own, inappropriate technique.

Chromosomal abnormalities in the first and second polar body.

Aneuploidy free oocytes may be pre-selected by testing the first and second polar bodies removed from oocytes following their maturation and fertilization. We present here our experience on the application of the method in IVF cycles from patients of advanced maternal age. Overall, 5590 oocytes were obtained from 917 cycles and tested by polar body sampling and fluorescent in situ hybridization (FISH) analysis using specific probes for chromosomes 13,16,18,21 and 22. FISH results were available in 4599 (82.2%) of 5590 oocytes studied, from which 2077(45.2%) were with aneuploidies. Thirty six point one percent of aneuploidies were of the first meiotic origin, and 29.3% of the second meiotic origin. Most errors in the first meiotic division were represented by chromatid errors. The transfer of embryos deriving from 2014 of 2520 aneuploidy free oocytes in 821 treatment cycles resulted in 182 (22.2%) clinical pregnancies and 140 healthy children born after confirmation of the polar body diagnosis. Polar body testing of oocytes provides an approach for pre-selection of aneuploidy free embryos, improving pregnancy rate in IVF patents of advanced maternal age.

How to predict recurrent shoulder dystocia.

OBJECTIVE: Our aim was to determine the rate and risk factors for recurrent shoulder dystocia. STUDY DESIGN: A retrospective analysis of patients diagnosed with shoulder dystocia was performed by searching a computerized database from January 1, 1993, to June 30, 1999 for the following information: (1) vaginal deliveries, either spontaneous or operative, (2) shoulder dystocia, (3) birth weight, (4) duration of second stage of labor, (5) parity, and (6) gestational diabetes. Statistical analyses included chi(2) and t test. RESULTS: There were 39,681 vaginal deliveries with 602 (1.5%) complicated by shoulder dystocia. Sixty-six patients underwent a subsequent vaginal delivery, and 11 (16.7%) experienced another shoulder dystocia. The odds ratio for a recurrent shoulder dystocia was 10.98 (P <.000001). Nine of the 11 patients with recurrent shoulder dystocia compared with 28 of 55 without a recurrence were nulliparous women in their index pregnancy (P <.001). The mean fetal weights were 3885 g in the recurrent dystocia group and 3702 g in the group without recurrence (P <.03). Gestational age, operative delivery, and gestational diabetes were similar in the two groups. CONCLUSION: Factors that appear to increase the recurrence risk of shoulder dystocia include fetal weight and maternal parity. Prior shoulder dystocia is the single greatest predictive factor.

The quantum origins of the free induction decay signal and spin noise.

Experiments are described that elucidate the quantum mechanical origins of the free induction decay voltage and of spin noise. It is shown that the experimentally measured FID voltage induced in a Hertzian loop receiving coil following a 90 degrees pulse is typically two orders of magnitude too large to be accounted for by the current quantum theory of signal reception-coherent spontaneous emission. An experiment is then presented in which spin noise is easily observed in a circuit with a Q-factor of order unity, thereby undermining a popular hypothesis that such noise is due to spontaneous emission and is only observable because of the enhancement in the density of the radiation field in a high Q-factor tuned circuit, the NMR probe. Both the free induction decay and the spin noise are shown to be accurately predicted by near-field Faraday induction, which is described in the theory of quantum electrodynamics by an exchange of virtual photons. A heuristic approach to understanding the nature and role of virtual photons in the signal reception process is then given. Thus current popular statements that observation of the magnetic resonance phenomenon relies on the absorption and emission of radio waves are shown to be wrong.

Crown-rump lengths in missed miscarriages and trisomy 21.

OBJECTIVES: To compare crown-rump lengths with karyotypes of missed miscarried fetuses and to determine a relationship between crown-rump length and trisomy 21. STUDY DESIGN: Chorionic villus sampling was performed on 129 consecutive missed miscarriages between 10 and 12 weeks by last menstrual period in patients >or= 35 years of age. Crown-rump length was correlated with the karyotype. Statistical analysis was performed using Student's t-test. RESULTS: Twenty-one of 129 missed miscarriages involved fetuses affected by trisomy 21. The crown-rump length was < 22 mm in 77% of missed miscarriages. Using a crown-rump length of >or= 22 mm for the prediction of trisomy 21 had a sensitivity of 86%, specificity of 89%, positive predictive value of 60% and negative predictive value of 97%. At 10-12 weeks, the crown-rump lengths of missed miscarried fetuses with trisomy 21 was significantly larger (P or= 35 years of age, with a missed miscarriage, in whom pregnancies reached >or= 10 weeks from the last menstrual period, a fetal crown-rump length of >or= 22 mm has a high probability that the etiology of the loss will be secondary to trisomy 21.

Effect of lamellar flap location on corneal topography after laser in situ keratomileusis.

PURPOSE: To investigate the effect of hinge position on corneal topography after laser in situ keratomileusis (LASIK) for myopia. SETTING: Academic center and refractive surgery practice. METHODS: Topography data obtained from 89 eyes of 46 patients after LASIK were analyzed. Using a system of Cartesian coordinates, data along the horizontal and vertical axes were analyzed, measuring sagittal height and power change at 1 mm intervals from the ablation zone center. Data points that were equidistant and on opposite sides of the ablation center were compared to find asymmetry along either axis relative to nasally hinged flaps. RESULTS: Along the horizontal axis, areas of the cornea closer to the hinge had a higher topography than areas farther from the hinge. Specifically, the points nearest and farthest from the hinge were significantly different in sagittal height (P <.034); the areas farthest from the hinge were reduced more after surgery (relatively lower topography). When results were stratified into low- and high-diopter corrections, this difference was significant in only the high-diopter group (P <.0006). Trends in power change were also observed. Areas of the cornea closer to the hinge were relatively flatter than areas farther from the hinge. Statistical significance was detected in only the low-diopter group at data points 2 mm from the ablation zone center in opposite directions (P <.008). No asymmetry was seen along the vertical axis in power change or sagittal height. CONCLUSIONS: The lamellar flap in LASIK may influence postoperative corneal topography. Hypothetically, the corneal flap may retract toward the hinge, producing axial asymmetry in the postoperative topography relative to the hinge. Understanding the influence of corneal flap characteristics on post-LASIK topography may improve optical results and may be particularly important in the development and effectiveness of topography-guided ablation techniques.

Body composition assessed by neutron activation analysis in dialysis patients.

Malnutrition is prevalent in end-stage renal disease (ESRD) patients treated with hemodialysis (HD) and peritoneal dialysis (PD). In addition, there is increased incidence of morbidity in this group. Evaluation of nutritional status is important. Application of body composition in the ESRD population to evaluate body compartments and to assess nutritional health has become more common in clinical practice. Neutron activation analysis (NAA) may provide data on metabolically active tissue by quantification of total body potassium (TBK) for body cell mass and assessment of protein by total body nitrogen (TBN). This method may be able to detect changes in body composition before clinical signs of malnutrition are apparent. Ten HD (5 male and 5 female) and 10 PD patients (7 male and 3 female) were evaluated by NAA, TBK, and isotope dilution. Female PD patients had an increased total body water (TBW) and increased intracellular water compared to HD females. Albumin was lower in PD women. There was no significant difference between PD men and laboratory controls in TBW, extracellular water, and TBN. The clinical application of body composition methods for evaluation of dialysis patients by serial assessment and for development of a bedside tool needs further study.

Obstetric outcomes in 102 pregnancies after preimplantation genetic diagnosis.

OBJECTIVE: We sought to determine whether preimplantation genetic diagnosis is associated with particular pregnancy or delivery complications. STUDY DESIGN: A total of 102 consecutive pregnancies after preimplantation genetic diagnosis by polar body removal performed at Illinois Masonic Medical Center resulting in 114 live births were analyzed. All patients were given a delivery and newborn questionnaire, and attempts were made to contact and question them regarding any pregnancy complications and type of delivery. Permission was obtained to examine medical records and discuss the patient's pregnancy with her obstetrician when questions existed with respect to complications or indication for cesarean delivery. RESULTS: Delivery and newborn questionnaires were completed or telephone contact was achieved for 100 of the 102 pregnancies. There were 85 singleton, 9 twin, and 7 triplet pregnancies. Of the 7 triplet gestations, 3 couples elected multifetal pregnancy reduction to twins and healthy triplets were born to 4 couples between 32 and 36 weeks by cesarean delivery. Of the 80 singleton deliveries, 60 (75%) progressed to term. Of these 60 term singleton deliveries, 34 were vaginal, 23 were cesarean (40%), and 3 delivery types were unknown. The incidence of small-for-gestational-age infants was 3% for neonates in the 60 term singleton deliveries and 7% in the entire cohort of 80 singleton deliveries. Only 3 pregnancy complications (other than premature delivery) were reported more than once. There were 3 instances each of gestational diabetes, intrauterine growth restriction, and pregnancy-induced hypertension. There was 1 case each of HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, congestive heart failure, mild oligohydramnios, and abruptio placentae. The indications for cesarean delivery were (in descending order) failure of labor to progress (n = 7), fetal distress (n = 4), placenta previa (n = 4), elective repeat cesarean delivery (n = 4), triplets (n = 3), uterine scarring (n = 3), 1 twin in the breech position (n = 3), failed forceps delivery (n = 2), and a variety of other indications that occurred in only 1 patient each. All preimplantation genetic diagnoses were confirmed by prenatal or postnatal testing. No diagnostic errors were made in this cohort of patients or in any patients undergoing preimplantation genetic diagnosis having polar body removal in our center. CONCLUSIONS: Preimplantation genetic diagnosis is associated with a risk of multiple gestations, cesarean delivery, and placenta previa. Cesarean delivery rates and multiple gestation rates are comparable to those of patients undergoing in vitro fertilization in general. The preimplantation genetic diagnosis itself does not seem to cause an increased risk for any particular pregnancy complication, with the possible exception of placenta previa, which was seen in 4% of patients.

Photorefractive keratectomy for myopia with a 15 Hz repetition rate.

PURPOSE: To evaluate excimer laser photorefractive keratectomy (PRK) for myopia using a repetition rate of 15 Hz instead of 10 Hz. SETTING: The Cornea and Laser Eye Institute, Teaneck, and Department of Ophthalmology, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA. METHODS: Photorefractive keratectomy using a 15 Hz repetition rate was performed in 23 eyes of 14 patients by a single surgeon at 1 center. The attempted corrections ranged from -2.8 diopters (D) to -5.5 D. Preoperative and postoperative uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), predictability, corneal haze, and subjective glare/halo were evaluated over 6 months. RESULTS: At 6 months, UCVA was 20/32 or better in all eyes and at least 20/20 in 14 eyes (73.7%). Two eyes (10.5%) lost 2 or more Snellen lines of BSCVA; postoperative BSCVA was at least 20/25 in 100% of eyes and 20/20 or better in 95.0%. Fifteen eyes (78.9%) were within +/-0.5 D of attempted correction, and 19 (100%) were within +/-1.0 D. Mean spherical equivalent refraction was -4.62 D preoperatively, +0.15 D at 1 month, -0.09 D at 3 months, and -0.37 D at 6 months. At 6 months, 4 eyes (21.0%) had no corneal haze and 14 (73.7%) had trace subepithelial haze. Fifteen eyes (78.9%) had no glare/halo effect at 6 months, and 4 (21.0%) had minimal glare/halo effect. CONCLUSIONS: Clinical outcomes after excimer laser PRK for myopia using an increased repetition rate of 15 Hz were good and similar to those in studies conducted with a 10 Hz repetition rate.

Prevention of age-related aneuploidies by polar body testing of oocytes.

PURPOSE: We previously demonstrated that aneuploidy-free oocytes may be preselected by testing the first and second polar bodies removed from oocytes following their maturation and fertilization. The present paper describes the results of the application of the method in 659 in vitro fertilization cycles from patients of advanced maternal age. METHODS: Using micromanipulation techniques, 3943 oocytes were tested by polar body sampling and fluorescent on situ hybridization analysis using specific probes for chromosomes 13, 18, and 21. RESULTS: Fluorescent in situ hybridization results were available for 3217 (81.6%) of 3943 oocytes studied, of which 1388 (43.1%) had aneuploidies; 35.7% of the aneuploidies were of first meiotic division origin, and 26.1% of second meiotic division origin. Most errors in the first meiotic division were represented by chromatid malsegregation. The transfer of embryos deriving from 1558 of 1829 aneuploidy-free oocytes in 614 treatment cycles resulted in 131 clinical pregnancies and 88 healthy children born after confirmation of the polar body diagnosis. CONCLUSIONS: Polar body testing of oocytes provides an accurate and reliable approach for prevention of age-related aneuploidies in in vitro fertilization patients of advanced maternal age.

Prenatal diagnosis of 46,XX male fetuses.

Ultrasonography can accurately determine phenotypic sex differences from those of the genetic sex. Two cases were identified; they were the result of a translocation of the SRY gene from the Y chromosome to the X chromosome during meiosis. An ultrasonographic difference may represent an otherwise unsuspected genetic abnormality.

Percentage body fat determination in hemodialysis and peritoneal dialysis patients: a comparison.

OBJECTIVE: To evaluate percentage body fat in hemodialysis (HD) and peritoneal dialysis (PD) patients. DESIGN: A prospective study of 20 HD patients and 20 PD patients. SETTING: Sol Goldman Renal Therapy Center, Lenox Hill Hospital, New York, NY; Baumritter Kidney Center Albert Einstein College of Medicine, Bronx, NY; Body Composition Unit, St Luke's Roosevelt Hospital, Columbia University, New York, NY. PATIENTS: Twenty HD (10 men, 10 women) patients, mean age 41.8 +/- 2.4 years and 20 PD (12 men, 8 women) patients, mean age 48.6 years +/- 3.0 years. INTERVENTION: This is a noninterventional study. PATIENTS signed consent to undergo dual-energy x-ray absorptiometry, total body potassium counting bioelectrical impedance analysis, total body water determination, and anthropmetric evaluation. MAIN OUTCOME MEASURES: Present and compare percentage body fat between HD and PD patients as determined by the methods used. RESULTS: Percentage fat is not different between HD and PD patients. Differences in absolute values of percent fat between techniques exist. CONCLUSION: HD patients and PD patients may be evaluated by the methods of body composition used. Percentage body fat will vary among techniques; therefore the same method should be used to follow a patient over time.

Three births after preimplantation genetic diagnosis for cystic fibrosis with sequential first and second polar body analysis.

OBJECTIVE: The purpose of this study was to determine the accuracy and feasibility of sequential polar body removal and analysis for preimplantation genetic diagnosis of mendelian disorders. STUDY DESIGN: Three couples with risk factors for cystic fibrosis had preimplantation genetic diagnosis with the use of sequential polar body analysis. After stimulation, oocytes were harvested and the first polar bodies were removed and analyzed on the day of aspiration. The following day, after fertilization, the second polar bodies were aspirated. Only embryos known to have inherited the normal maternal allele were transferred. RESULTS: All three couples had successful pregnancies resulting in the births of unaffected infants. CONCLUSIONS: Preimplantation diagnosis with the use of sequential polar body removal is feasible and can prevent the establishment of genetically abnormal pregnancies for couples at risk.

Detection of translocations involving the Y-chromosome in prospective prenatal screening of common chromosomal aneuploidies by FISH.

In the application of the fluorescence in situ hybridization (FISH) technique for prospective prenatal screening of common aneuploidies involving the autosomes 13, 18, and 21, and sex chromosomes, six cases of inconsistency between the results of FISH analysis and the results of karyotyping of cultured amniocytes have been observed, including two cases of translocation involving the Y-chromosome and chromosome 15 in a total of 904 cases of amniocentesis studied. In one case, the translocation was of maternal origin, and in the other, of paternal origin. In both cases, the couples decided to continue the pregnancy and normal babies were delivered. The data show the usefulness of applying the FISH technique in prospective prenatal screening of common trisomies for the possible detection of rare chromosome rearrangements involving the Y-chromosome.

Preimplantation diagnosis of common aneuploidies by the first- and second-polar body FISH analysis.

PURPOSE: A low pregnancy rate in in vitro fertilization (IVF) patients of advanced maternal age may be caused by aneuploidies originating from non disjunction in the first or second meiotic divisions. We introduced genetic testing of oocytes by sampling and fluorescent in situ hybridization (FISH) analysis of the first and second polar bodies, to avoid fertilization and transfer of aneuploid oocytes in IVF patients of advanced maternal age. METHODS: Three hundred and sixty-three IVF patients 34 years and older participated in the study. Using micromanipulation procedures, the first and second polar bodies were removed following their extrusion from the oocytes and studied by FISH, using probes specific for chromosomes 13, 18, and 21 to detect oocytes with common aneuploidies. RESULTS: Of a total of 538 IVF cycles, 3250 oocytes were available for FISH analysis, with conclusive FISH results in 2742 oocytes (84.3%). As many as 1102 (40%) of oocytes were predicted to be aneuploid and not transferred. Of 1640 embryos predicted to be normal, 1145 were transferred in 467 treatment cycles, resulting in 107 pregnancies (23%), from which 67 healthy children have been born, 32 pregnancies spontaneously aborted, and 15 pregnancies are ongoing after being confirmed normal by prenatal diagnosis. CONCLUSIONS: Preimplantation diagnosis by first- and second-polar body FISH analysis allows us to avoid the age-related risk of common aneuploidies in IVF patients of advanced maternal age.

Sex difference in crown-rump length in first-trimester twins.

OBJECTIVE: To determine if there is a difference in the crown-rump length (CRL) between male and female fetuses in the first trimester. STUDY DESIGN: CRL was determined in 77 normal twin pairs at the time of chorionic villus sampling. The sex of each fetus was assigned based upon the results of the sampling. RESULTS: A small difference was found between the CRL of males as compared to females, but this was not statistically significant. However, if there was a difference in size between the twin pairs, the odds were 1.5:1 that the larger would be male. CONCLUSION: There is no clinically significant difference in size between male and female fetuses in the first trimester of pregnancy.

Association of parvovirus infection with isolated fetal effusions.

The association of parvovirus B19 infection and hydrops fetalis is well known. However, the association of parvovirus and fetal pleural or pericardial effusions has not been reported. We present five cases of isolated pleural or pericardial effusion with documented maternal parvovirus infection in four of these pregnancies. In the absence of structural or karyotypic abnormalities, spontaneous resolution of the effusion portends for a successful pregnancy outcome.