Javier Miguelez

Prognostic factors associated with congenital cystic adenomatoid malformation of the lung

This study presents 18 cases of prenatally diagnosed congenital cystic adenomatoid malformation (CCAM) to identify potential factors that could predict prognosis. Comparisons of prenatal parameters were made between fetuses that survived and those that died perinatally. It was found that microcystic lesion, bilateral lung involvement and hydrops were each highly correlated with poor prognosis, while neither polyhydramnios nor mediastinal shift was significantly associated with had outcome. Fetal interventions were indicated only in two of the surviving cases: a thoracocentesis and a cysto‐amniotic shunt. A therapeutic amniocentesis was performed in one case of polyhydramnios. The diagnosis of CCAM was histologically confirmed in all cases by necropsy or by postnatal lobectomy. Copyright

Fetal nasal bone length: reference range and clinical application in ultrasound screening for trisomy 21

Fetuses with trisomy 21 typically present with subtle facial abnormalities, including a hypoplastic nasal bone. The aim of this study was to provide a reference range for the length of the fetal nasal bone and to test its value in second‐trimester ultrasound screening for trisomy 21.

Fetal renal biopsies in obstructive uropathy: feasibility and clinical correlations—preliminary results

Final assessment on the outcome of fetal obstructive uropathy is a challenging matter. Ultrasonography, fetal urine electrolytes, and beta 2 microglobulin are postulated as being useful in many cases. For cases in which renal function remains unclear, ultrasound‐guided fetal kidney biopsy may be used in order to detect histologic features distinctive of renal dysplasia. We present preliminary results aimed at studying the feasibility and possible risks. Biopsies were initially performed in 11 severely malformed fetuses, three of them with associated renal abnormalities. The success rate in obtaining renal material was 63·6 per cent with no maternal complications. In the next phase of this study, ten biopsies and urine collections were performed in fetuses with bilateral obstructive uropathy. The success rate was 50 per cent with no complications. Normal fetal renal histology was seen in 80 per cent of cases. In one case, although electrolytes were normal, a histologic diagnosis of renal dysplasia was made, showing a good correlation with outcome. In conclusion, fetal kidney biopsies for obstructive uropathy are feasible and further studies are needed to show their clinical relevance and risks.

Second-trimester soft markers: relation to first-trimester nuchal translucency in unaffected pregnancies

Genetic sonography following first‐trimester combined screening appears to increase substantially detection rates for Down syndrome but it relies on the unproved assumption of independence between these tests. In this study we aimed to investigate the relationship between first‐trimester nuchal translucency (NT) and a series of second‐trimester soft markers and structural defects in unaffected pregnancies.

Ultrasound detection rate of single umbilical artery in the first trimester of pregnancy.

To determine accuracy of first trimester detection of single umbilical artery (SUA).

Fetal tricuspid valve Doppler at 11–13 weeks and 6 days: reference values and reproducibility

To determine normal blood flow velocities across the fetal tricuspid valve (TV) at 11–13 weeks and 6 days of gestation and to examine the reproducibility of these measurements.

Rastreamento Antenatal da Síndrome de Down Utilizando Parâmetros Ultra-sonográficos

Purpose: to appraise the value of ultrasonographic parameters for the diagnosis of fetal Down syndrome (T21), in order to permit its use in routine clinical practice. Methods: this is a prospective cohort study using various ultrasonographic parameters for the prediction of T21. A total of 1662 scans were evaluated in the cohort study and 289 examinations were analyzed as a differential sample to test the normality curve from October 1993 to November 2000. The statistical analysis was based on the calculation of intra- and interobserver variations, the construction of normality curves for the studied parameters, as well as their validity tests, and the calculation of sensitivity, specificity, relative risk, likelyhood ratio and posttest predictive values. Results: among 1662 cases, 22 fetuses (1.32%) with T21 were identified. The normality curves were built for nucal fold thickness, femur/foot ratio and nasal bone length. Renal pelvis had a semiquantitative distribution and the proposed cutoff level was 4.0 mm. Sensitivity, specificity, false positive rate, relative risk and likelyhood ratio for nucal fold measurements above the 95th percentile were 54.5%, 95.2%, 4.9%, 20.2 and 11, respectively. For nasal bone measurements below the 5th percentile, 59.0%, 90.1%, 9.0%, 13.4 and 6.5. For femur/foot ratio below the 5th percentile, 45.5%, 84.4%, 15.6%, 3.7 and 2,6. For renal pelvis greater than 4.0 mm, 36.4%, 89.2%, 10.9%, 4.5 and 3.4. For absent fifth finger middle phalanx, 22.7%, 98.1%, 1.9%, 13.2 and 11.9. For the presence of major malformations, 31.8%, 98.7%, 1.3%, 27.2 and 24,8. After calculating the probability rates and the incidence of T21 in different maternal ages, a table for posttest risk using ultrasonographic parameters was set up. Conclusions: normality curves and indices for the assessment of risk for fetal Down syndrome on a population basis were established by the utilization of different maternal ages and by multiplying factors proposed by the authors. It was not possible to establish a normality curve for renal pelvis measurements, because of their semiquantitative distribution.

Isochromosome 21q is overrepresented among false-negative cell-free DNA prenatal screening results involving Down syndrome

False-negative cell-free DNA (cfDNA) screening results involving Down syndrome are rare, but have high clinical impact on patients and their healthcare providers. Understanding the biology behind these results may allow for improved diagnostic follow-up and counseling. In 5 different centers offering cfDNA prenatal screening, 9 false-negative results were documented in 646 confirmed cases of trisomy 21; a false-negative rate of 1.4% (95% CI, 0.7–2.6). False-negative results included 4 cases of classical trisomy 21 and 5 cases with a de novo 21q;21q rearrangement. Two out of five rearrangements had molecular studies and were confirmed as isochromosomes. When combined with reports from the cfDNA screening literature, 8 out of 29 (28%) Down syndrome cases with a false-negative “non-invasive prenatal test” (NIPT) were associated with a 21q;21q rearrangement, compared with 2% reported in live born children with Down syndrome. In our laboratory series, evidence for placental or fetal mosaicism was present in 3 out of 3 true-positive cases involving a 21q;21q rearrangement and was confirmed in one false-negative case where placental material was available for study. Isochromosome 21q rearrangements are thus overrepresented among false-negative cfDNA screening results involving Down syndrome. Postzygotic isochromosome formation leading to placental mosaicism provides a biological cause for the increased prevalence of these rearrangements among false-negative cases. For clinical practice, a low trisomic fraction (z-score or equivalent measure) relative to the fetal fraction suggests placental mosaicism. Care should be taken as these cases may not reflect confined placental mosaicism, but rather full trisomy in the presence of a placenta containing normal cells.

Diagnóstico pré-natal das genodermatoses

Prenatal diagnostic testing is indicated for some severe genodermatoses, such as recessive dystrophic epidermolysis bullosa and junctional epidermolysis bullosa. Fetal skin biopsy was introduced in 1980, but it cannot be performed before 15th gestational week. Fetal DNA analysis is a precise method and can be performed earlier in pregnancy. However, the molecular basis of the genodermatoses must be known and it is essential to determine the gene mutations and/or informative markers in the families with a previously affected child. Fetal DNA can be obtained by chorionic villus sampling or amniocentesis. Preimplantation genetic diagnosis is an alternative approach obviating the need for termination of pregnancy. It involves in vitro fertilization and genetic testing of embryos. However, this technique has been performed for genodermatoses in only a few reference centers. Ultrasonography is a non-invasive test, but has a limited use in prenatal diagnosis of genodermatoses. Tridimensional ultrasonography usually establishes diagnosis late in pregnancy and there are only anecdotal reports of prenatal diagnosis of genodermatoses using this method.

Determinação ultra-sonográfica do sexo fetal pela medida dos ângulos do apêndice genital

PURPOSE: to evaluate the accuracy of fetal gender prediction at 11 to 13 weeks and 6 days by measuring the anterior and posterior genital tubercle angles. MESTHODS: the anterior and posterior genital tubercle angles were measured in a midsagittal plane in 455 fetuses from 11 to 13 weeks and 6 days. The probability of a correct fetal sex prediction (confirmed after birth) was categorized in accordance with the angle measurements, gestational age and crump-rump length. The optimal accuracy cutoffs were derived from a ROC-plot. The interobserver variability was evaluated by a Bland-Altman plot. RESULTS: the correct fetal sex prediction rate increased with gestational age and crump-rump length. Using a 42-degree anterior angle as a cutoff, a correct fetal sex prediction occurred in 72% of the fetuses from 11 to 11 weeks and 6 days, 86% from 12 to 12 weeks and 6 days and 88% from 13 to 13 weeks and 6 days. Using a 24-degree posterior angle as a cutoff, a correct fetal gender prediction occurred in 70, 87 and 87%, respectively. The interobserver variability evaluation revealed a mean difference between paired measurements of 15.7 and 9 degrees for the posterior and anterior angles, respectively. CONCLUSION: the measurement of the genital tubercle angles showed a high accuracy in correctly predicting the fetal sex from the 12th week of gestation on. However, accuracy was still not high enough for clinical use in pregnancies at risk of serious X-linked diseases.