Fetal blood sampling and cytogenetic abnormalities

From September 1984 to April 1991, we performed cytogenetic analysis on fetal blood samples from 214 second-and third-trimester pregnancies. One hundred and thirty-four cases were referred to consider the possibility of chromosomal mosaicism following amniocyte studies. The confirmation rate of mosaicism is at 0 per cent (0/9), 1·4 per cent (1/70), and 40 per cent (22/55) for cases of level I, level II, and level III mosaicism, respectively. Four out of 17 cases were positive for the diagnosis of fragile X syndrome. Of 63 cases with abnormal ultrasound findings, blood disorders, or other genetically related clinical conditions, 11 were found to have a chromosome abnormality. Fetal blood sampling is a valuable adjunct to other methods in the prenatal diagnosis of chromosomal mosaicism or pseudomosaicism. It is also useful when rapid cytogenetic diagnosis is desired because of malformations detected in pregnancies at a late gestational age.     

Ultrasound diagnosis of fetal abnormalities and cytogenetic evaluation

Over a 65½ year period, in 288 pregnancies a variety of fetal malformations were detected by ultrasound. Two hundred and ten fetuses (73 per cent) were karyotyped. Gestational age at detection ranged from 11 to 38 weeks. The incidence of an abnormal karyotype in the total series was 14 per cent and 14.7 per cent in the 210 pregnancies in which a karyotype was performed. Single structural anomalies were found in 149 cytogenetically investigated fetuses, of which 25 had a chromosomal abnormality (17 per cent). Multiple structural malformations were present in 61 fetuses, of which 16 had an abnormal karyotype (26 per cent). Trisomy 18 was the most frequent finding. The most constant ultrasound finding in cases of an abnormal karyotype was polyhydramnios and severe IUGR in combination with structural defects. There is a need for extensive detailed ultrasound examination in high-risk pregnancies.     

Prenatally detected trisomy 4 and 6 mosaicism—cytogenetic results and clinical phenotype

We report on a live-born male with 46,XY/47,XY+4/47,XY,+6 mosaicism. Trisomy 4 mosaicism was detected by karyotyping chorionic villus samples (CVS) and was confirmed by the analysis of 16 metaphases obtained from cultured amniotic fluid cells. Eight metaphases were normal (46,XY), two had trisomy 4 (47,XY,+4), and two had trisomy 6 (47,XY,+6). Two postnatal chromosomal analyses of blood lymphocytes at birth and at the age of one week were normal. Chromosomal analysis of cultured skin fibroblasts from the right inguinal region at the age of 12 months revealed trisomy 4 (47,XY,+4) in 49 metaphases, trisomy 6 (47,XY,+6) in 2 metaphases, and a normal karyotype (46,XY) in 49 cells of the 100 analyzed metaphases, respectively. The main clinical findings consist of prenatal growth retardation, hypoplasia of the right side of the face, a dysplastic and posteriorly rotated right ear, a high vaulted palate, retrognathia, aplasia of the right thumb, hypoplasia of the fingernails, a deep sacral dimple, and patchy skin hypopigmentation of the right leg. When last seen at the age of 14 months, his development was nearly normal. Five patients with trisomy 4 mosaicism have been reported previously, but none with an additional trisomy 6 mosaicism. Copyright © 2003 John Wiley & Sons, Ltd.     

Fetoplacental discrepancy involving structural abnormalities of chromosome 8 detected by prenatal diagnosis

We describe the finding of three cell lines involving different structural abnormalities of chromosome 8 detected in a prenatal diagnosis. Chorionic villi sampling (CVS) was performed on a pregnant woman because of advanced maternal age. Semidirect cytogenetic analysis showed a mos46,XX,i(8q)/46,XX,del(8)(p11.2) karyotype, confirmed by fluorescence in situ hybridization (FISH). Amniocentesis was subsequently performed, and the karyotype obtained was 46,XX,dup(8)(p23p11.2). The pregnancy was terminated; pathologic findings included clubfeet, clenched left hand, subcutaneous edema and bilateral hydrocephalus. Molecular studies using chromosome 8 microsatellites performed on parents' blood and fetal tissues revealed a maternal meiotic origin of the inv dup(8p) with deletion of the distal p23 region and duplication of the remaining 8p. We propose a model to explain the cytogenetic findings, which includes a first maternal meiotic error giving rise to a large dicentric isochromosome 8 present in the ovum, a second error in one of the first zygote divisions with misdivision of the dicentric 8 giving rise to a cell line with del(8p) confined to the trophoblast and another cell line with inv dup(8p) confined to the fetal tissue and a third error in the trophoblast giving rise to a further cell line with isochromosome 8q. Copyright © 2003 John Wiley & Sons, Ltd.     

Residual risk for cytogenetic abnormalities after prenatal diagnosis by interphase fluorescence in situ hybridization (FISH)

Results from conventional cytogenetic studies on 21 609 amniotic fluid specimens were analyzed retrospectively to determine the residual risk for a cytogenetic abnormality if interphase FISH, capable of only detecting aneuploidy for chromosomes 13, 18, 21, X and Y, was performed and did not reveal an abnormality. Detection rates (the probability of detecting a cytogenetic abnormality when an abnormality is present) and residual risks (the likelihood of a cytogenetic abnormality, in view of normal interphase FISH results) were calculated for the four major clinical indications for prenatal diagnosis (advanced maternal age, abnormal maternal serum screen indicating increased risk for trisomy 18 or trisomy 21, abnormal maternal serum screen indicating increased risk for neural tube defects and ultrasound abnormality). Differences in detection rates were observed to depend on clinical indication and presence or absence of ultrasound abnormalities. The detection rate ranged from 18.2 to 82.6% depending on the clinical indication. The detection rates of abnormalities significant to the pregnancy being evaluated (i.e. abnormalities excluding familial balanced rearrangements and familial markers) were between 28.6 and 86.4%. The presence of ultrasound abnormalities increased the detection rate from 72.2 to 92.5% for advanced maternal age and from 78.6 to 91.3% for abnormal maternal serum screen, indicating increased risk for trisomy 18 or trisomy 21. With regard to residual risk, the risk for a clinically significant abnormality decreased from 0.9–10.1%, prior to the interphase FISH assay, to a residual risk of 0.6–1.5% following a normal interphase FISH result in the 4 groups studied. Providing patients with detection rates and residual risks, most relevant to their situation (clinical indication and presence or absence of ultrasound abnormality) during counseling, could help them better understand the advantages and limitations of interphase FISH in their prenatal diagnostic evaluation. Copyright © 2003 John Wiley & Sons, Ltd.     

Trisomy 5 mosaicism detected prenatally with an affected liveborn

This paper reports a case of chromosomal mosaicism for trisomy 5 recovered from amniotic fluid cells and from skin fibroblasts of a liveborn dysmorphic male. Routine amniocentesis was performed at 16 weeks' gestation because of parental concern. Trisomy 5 cells were measured from 25 per cent of amniocytes from two culture vessels. No further invasive testing was performed until 32 weeks' gestation, at which time ultrasound examination showed fetus with intrauterine growth retardation. Fetal blood sampling was then performed, with only karyotypically normal cells recovered. At birth, the child was found to have multiple dysmorphic features and congenital anomalies, including an eventration of the diaphragm and ventricular septal defect, both of which required surgical correction. Chromosomal analysis of cord blood lymphocytes indicated 46,XY; however, 20 per cent of the cultured fibroblasts obtained from the chest skin at the incision site for diaphragmatic repair had a 47,XY,+5 karyotype. Trisomy 5 mosaicism may be another example of tissue-limited mosaicism. Fetal blood sampling can then be falsely reassuring. Furthermore, because some cell lines rarely appear in lymphocyte populations, cytogenetic analysis of multiple tissues warranted as part of the evaluation of individuals with developmental delay and dysmorphic features.     

Current controversies in prenatal diagnosis 2: Cell-free DNA prenatal screening should be used to identify all chromosome abnormalities

Noninvasive prenatal testing (NIPT) using cell-free DNA (cfDNA) from maternal serum has been clinically available since 2011. This technology has revolutionized our ability to screen for the common aneuploidies trisomy 21 (Down syndrome), trisomy 18, and trisomy 13. More recently, clinical laboratories have offered screening for other chromosome abnormalities including sex chromosome abnormalities and copy number variants (CNV) without little published data on the sensitivity, specificity, and positive predictive value. In this debate, the pros and cons of performing prenatal screening via cfDNA for all chromosome abnormalities is discussed. At the time of the debate in 2017, the general consensus was that the literature does not yet support using this technology to screen for all chromosome abnormalities and that education is key for both providers and the patients so that the decision-making process is as informed as possible.     

MARPOL 73／78附则Ⅰ第13G条修正情况及对中国影响分析

通过对国际海事组织海上环境保护委员会召开有关会议修订了MARPOL 73／78附则Ⅰ第13G条情况的介绍，综合分析了13G条新修正案对中国的影响，并提出相应的建议。     

《73/78防污公约》附则Ⅳ实施对策

《73/78防污公约》附则Ⅳ将于2003年9月27日生效。根据MEPC88（44）号决议，所有缔约国在附则Ⅳ生效后都将立即执行经修正的附则Ⅳ。中国政府尚未批准附则Ⅳ，但中国批准和执行附则Ⅳ是大势所趋，为此，无论是航运单位还是海事部位，都要认真研究相应的对策并作好实施附则Ⅳ的相关准备工作。