Copy number imbalances detected with a BAC-based array comparative genomic hybridization platform in congenital diaphragmatic hernia fetuses.

Congenital diaphragmatic hernia (CDH) is a phenotypically and genetically heterogeneous disorder, with a complex inheritance pattern. Structural abnormalities of almost all chromosomes have been described in association with CDH. We made a molecular analysis through array comparative genomic hybridization (array CGH) of a group of fetuses with prenatal ultrasound diagnosis of CDH and normal G-banded karyotypes. A whole genome BAC-array CGH, composed of approximately 5000 BAC clones, was carried out on blood samples from fetuses with prenatal ultrasound diagnosis of CDH and a normal karyotype (500-band level). All potential cytogenetic alterations detected on the arrays were reported. The array CGH analysis showed copy number gains and losses in 10 of 12 cases. Eighty-five clones showed genomic imbalances, and 29 clones displayed described copy number variations. We identified a recurrent gain in 17q12 in two of 12 cases, which has not been previously described. Our results may contribute to determining the effectiveness and applicability of array CGH for prenatal diagnosis purposes, and also to elucidate the submicroscopic genomic instability of CDH fetuses.

Prenatal diagnosis of a partial trisomy 13q (q14-->qter): phenotype, cytogenetics and molecular characterization by spectral karyotyping and array comparative genomic hybridization.

Partial trisomy 13q is an uncommon chromosomal abnormality with variable phenotypic expression. We report prenatal diagnosis of partial trisomy 13q in a fetus with partial agenesis of the cerebellar vermis, partial agenesis of the corpus callosum, hydrops and polyhydramnios. G-banding karyotyping, spectral karyotyping and array comparative genomic hybridization (aCGH) analysis of fetal blood were performed. Cytogenetic analysis of fetal blood displayed 46,XX,add(4)(q28). The parental karyotypes were normal. A girl was delivered at 34 weeks gestation; she died within 2 h. Autopsy confirmed all the prenatal findings and also showed agenesis of the diaphragm. Spectral karyotyping identified the additional material's origin as chromosome 13. aCGH was carried out and showed amplification of distal regions of the long arm of chromosome 13 from region 13q14 to qter. This is the first report of a fetus with molecular characterization of a partial trisomy 13q (q14-->qter), present as a de novo unbalanced translocation at chromosome 4q. This case demonstrates the usefulness of molecular characterization of malformed fetuses for prenatal diagnosis and counseling.

Fetal thigh volumetry by three-dimensional ultrasound: comparison between multiplanar and VOCAL techniques.

OBJECTIVES: To evaluate the agreement between multiplanar and Virtual Organ Computer-aided AnaLysis (VOCAL()) techniques for the measurement of total fetal thigh volume and to assess the repeatability and reproducibility of measurements performed using these methods; to derive birth weight-predicting models for both methods and to compare their accuracies. METHODS: This was a cross-sectional study of 150 singleton pregnancies at 30-42 weeks of gestation in which ultrasound volumes of the fetal thigh were obtained within 48 hours of delivery and measured using multiplanar and VOCAL techniques. Bland-Altman analyses were performed to determine the agreement between the two methods, and to evaluate intraobserver and interobserver variability in a subset of 40 patients. Birth weight-predicting models were derived using total fetal thigh volumes obtained using the VOCAL (ThiV) and multiplanar (ThiM) methods as independent variables. The accuracies of these formulas were compared. RESULTS: The mean percentage difference between measurements performed using the VOCAL technique and the multiplanar technique was -0.04 and the 95% limits of agreement were -8.17 and 8.09. The mean percentage difference and 95% limits of agreement between paired measurements in the assessment of intraobserver and interobserver variability were -1.10 (-7.67 to 5.47) and 0.61 (-7.68 to 8.91) for the VOCAL technique and 1.03 (-6.35 to 8.41) and -0.68 (-11.42 to 10.06) for the multiplanar method, respectively. The best-fit formulas for predicting birth weight (BW) were: BW = 1025.383 + 12.775x ThiV; and BW = 1033.286 + 12.733x ThiM. There was no significant difference between the accuracies of these formulas. CONCLUSIONS: There is good agreement between the VOCAL and multiplanar techniques for assessment of total fetal thigh volume. Measurements performed using both methods are repeatable and reproducible. For prediction of birth weight, the formulas generated in this study can be used interchangeably.

Birth-weight prediction by two- and three-dimensional ultrasound imaging.

OBJECTIVES: To compare the accuracies of birth-weight predicting models derived from two-dimensional (2D) ultrasound parameters and from total fetal thigh volumes measured by three-dimensional (3D) ultrasound imaging; and to compare the performances of these formulae with those of previously published equations. METHODS: A total of 210 patients were evaluated to create a formula-generating group (n = 150) and a prospective-validation group (n = 60). Polynomial regression analysis was performed on the first group to generate one equation based on 2D ultrasound measurements, one based on fetal thigh volume measured by the multiplanar technique (ThiM) and one based on fetal thigh volume obtained by the Virtual Organ Computer-aided AnaLysis (VOCAL()) method (ThiV). Paired-samples t-tests with Bonferroni adjustments were used to compare the performances of these equations in the formula-finding and the prospective-validation groups. The same approach was used to compare the accuracies of the new 2D and 3D formulae with those of both original and modified 2D equations from previous publications, as well as the 3D model reported by Chang et al. RESULTS: The formulae with the best fit for the prediction of birth weight were: estimated fetal weight (EFW) = - 562.824 + 11.962x AC x FDL + 0.009 x BPD(2)x AC(2) (where AC is abdominal circumference, FDL is femur diaphysis length and BPD is biparietal diameter), EFW = 1033.286 + 12.733 x ThiM, and EFW = 1025.383 + 12.775 x ThiV. For both the formula-generating and the prospective-validation groups, there were no significant differences between the accuracies of the new 2D and 3D models in the prediction of birth weight. When applied to our population, the performances of the modified and original versions of the previously published 2D equations and the performance of the original 3D formula reported by Chang et al. were all significantly worse than our models. CONCLUSIONS: We believe that the greatest sources of discrepancy in estimation of birth weight are the phenotypic differences among patients used to create each of the formulae mentioned in this study. Our data reinforce the need for customized birth-weight prediction formulae, regardless of whether 2D or 3D measurements are employed.

Nuchal translucency: an ultrasound marker for fetal chromosomal abnormalities.

CONTEXT: The literature shows an association between several ultrasound markers and chromosome abnormality. Among these, measurement of nuchal translucency has been indicated as a screening method for aneuploidy. The trisomy of chromosome 21 has been most evaluated. OBJECTIVE: To define the best fixed cutoff point for nuchal translucency, with the assistance of the ROC curve, and its accuracy in screening all fetal aneuploidy and trisomy 21 in a South American population. TYPE OF STUDY: Validation of a diagnostic test. SETTING: This study was carried out at the State University of Campinas, Campinas, Brazil. PARTICIPANTS: 230 patients examined by ultrasound at two tertiary-level private centers, at 10 to 14 weeks of gestation. DIAGNOSTIC TEST: The participants consisted of all those patients who had undergone ultrasound imaging at 10 to 14 weeks of gestation to measure nuchal translucency and who had had the fetal or neonatal karyotype identified. MAIN MEASUREMENTS: Maternal age, gestational age, nuchal translucency measurement, fetal or neonatal karyotype. RESULTS: Prevalence of chromosomal defects - 10 %; mean age - 35.8 years; mean gestational age - 12 weeks and 2 days; nuchal translucency (NT) thickness - 2.18 mm. The best balance between sensitivity and specificity were values that were equal to or higher than 2.5 mm for overall chromosomal abnormalities as well as for the isolated trisomy 21. The sensitivity for overall chromosomal abnormalities and trisomy 21 were 69.5 % and 75 %, respectively, and the positive likelihood ratios were 5.5 and 5.0, respectively. CONCLUSION: The measurement of nuchal translucency was found to be fairly accurate as an ultrasound marker for fetal abnormalities and measurements equal to or higher than 2.5 mm were the best fixed cutoff points.

Anticardiolipin antibody in recurrent spontaneous aborting and fertile women.

OBJECTIVE: To determine the association between the presence of anticardiolipin antibody and a history of recurrent spontaneous abortion. STUDY DESIGN: Clinical controlled study. LOCATION: Department of Gynecology and Obstetrics-University of Campinas (UNICAMP). SUBJECTS: 52 individuals with recurrent spontaneous abortion were included in Group 1 and 104 individuals with at least one live born child in Group 2. Elapsed time from last delivery to blood sampling varied from six months to two years. METHOD: Between November 1993 and November 1994, patients' blood samples were screened for anticardiolipin antibody by ELISA, as described by Triplett, Barna and Unger (1993). ANALYSIS: Chi-square and Fisher's Exact tests were used for statistical analysis. Student's "t" test was used to compare the means. RESULTS: There was no statistical difference in the presence of the anticardiolipin antibody between Group 1 (zero and 2.9%) and Group 2 (7.7 and 5.8%). CONCLUSION: There was no association between the presence of anticardiolipin antibody and recurrent spontaneous abortion.

Placenta percreta with silent rupture of the uterus.

We report a case of placenta percreta diagnosed by ultrasound and color doppler image at the fourteenth week of gestation. Initial approach was a trial of IM methotrexate followed by total hysterectomy, during which was observed a rupture of the uterus with the adherence of the placenta to the posterior region of the bladder. We also present a literature review on the incidence of placenta percreta, etiology, diagnosis, treatment, and complications.

Multidisciplinary experience in the selection of patients for tubal sterilization.

Results of the use of a special protocol for evaluation of patients requiring tubal ligation is presented after applied by a multidisciplinary group. The authors conclude that the use of defined parameters of age, parity, marital union duration, number of children alive and the presence of maternal clinical pathology are useful to identify patients with smaller chances of regret after surgery.

PIP: 27% of reproductive-age women in Brazil have chosen surgical sterilization as their contraceptive method. Most of these women who have undergone tubal sterilization opted for cesarean surgery. However, given the young ages of many of these women, many regret having been sterilized. This paper summarizes the experience of a multidisciplinary group in evaluating women who apply for surgical sterilization at the Department of Tocogynecology, Faculdade de Ciencas Medicas, Universidade Estadual de Campinas in Sao Paulo. Detailed descriptions are presented of the medical and social characteristics of cases seen between June 1988 and July 1989. The authors conclude that the use of the defined parameters of age, parity, marital union duration, number of living children, and the presence of maternal clinical pathology are useful in identifying the patients who are least likely to regret undergoing surgical sterilization.

Down-regulation of maternal antiphospholipid antibodies during early pregnancy and pregnancy outcome.

OBJECTIVE: We investigated the hypothesis that maternal autoimmune responses to phospholipid antigens measured before and during pregnancy are not related to successful pregnancy outcome. STUDY DESIGN: One hundred twenty-three women with recurrent spontaneous abortions were serially tested for antiphospholipid antibodies during their pregnancies. RESULTS: In 72 women with recurrent spontaneous abortions and without antiphospholipid antibodies before the pregnancy, the incidence of antiphospholipid antibody production at the time of pregnancy termination was significantly higher in those who miscarried the index pregnancy than those who were delivered of a live-born infant. In 51 antiphospholipid antibody-positive women with recurrent spontaneous abortions there were dramatic increases in titers of anticardiolipin antibody and antiphosphatidylserine antibody in those who miscarried the index pregnancy (p < 0.005). In women who were delivered of a live-born infant, the titers remained stable or decreased during pregnancy. CONCLUSIONS: Down-regulation of antiphospholipid antibody production during early pregnancy is associated with favorable pregnancy outcome.

[Myasthenia gravis and pregnancy: review of the literature and report of 2 cases]. / Miastenia "gravis" e gravidez: revisão da literatura e relato de dois casos.

Two cases of women with myasthenia gravis are presented. These women had three pregnancies followed by the authors, and description is made of clinical follow-up, therapeutic complications, termination of pregnancy, puerperal and perinatal outcome. A review of the literature is made due to the rarity of this condition and emphasis is given to the specialized knowledge required to adequately manage these cases. Myasthenia gravis, when associated to pregnancy, presents aspects that make it a high risk disease, decompensations of myasthenia being more common. Aspects relative to diagnosis and therapy of myasthenia in pregnancy and in the newly-born are reviewed, and considerations about anesthesia in the myasthenic pregnant woman.

Programa de tocoginecologia preventiva.Plano piloto de medicina integral. / Program of preventive obstetrics and ginecology. Pilot plan of integral medicine

E importante conscientizar os estudantes de medicina e os medicos de que e mais adequado atender o paciente fazendo o que e necessario de forma simples e eficiente, sem perda de qualidade, de que atender de modo sofisticado a demanda manifestada sem olhar diversos aspectos organicos do paciente como um todos