Alpha-fetoprotein and acetylcholinesterase activity in first-and early second-trimester amniotic fluid

Normal ranges of amniotic fluid alpha-fetoprotein (AFP) and acetylcholinesterase activity (AChE) are described for gestational weeks 11–14 using rocket gel immunoelectrophoresis for AFP quantitation and a monoclonal antibody (4F19) enzyme antigen immunoassay for AChE activity measurement. The normal ranges were established by the examination of 281 amniotic fluid samples from 281 normal pregnancies. AFP was found to increase from a median level of 14.0 MIU/1 at 11 weeks to a maximum at 13 weeks (median=18.0 MIU/l) (P<0.05), thereafter falling (not significant). No AChE test result exceeded 4.8 nkat/l. In addition, AFP and AChE values for three cases of fetal malformation, identified by the biochemical analyses of amniotic fluid, are given. These cases included two fetuses with a neural tube defect and one fetus with an abdominal wall defect. Amniocentesis was performed at 10, 11, and 14 weeks, respectively. The AFP and AChE values were all high.     

Unexpected structural chromosome rearrangements in prenatal diagnosis

Among 5315 prenatal diagnoses performed for various indications (maternal age, neural tube defect, metabolic diseases, X-linked diseases, pathologic pregnancies) 29 unexpected structural chromosome rearrangements were found in fetal cells. Fourteen were de novo chromosome rearrangements, six unbalanced, and eight balanced. Fifteen were inherited and balanced rearrangements. This high frequency of structural anomalies is discussed.     

Open fetal surgery for myelomeningocele

Despite efforts at prevention through the use of preconception folic acid, spina bifida remains one of the most common congenital anomalies of the central nervous system that is compatible with life. It is, however, associated with a significant degree of lifelong morbidity. The development of open fetal surgery for myelomeningocele (MMC) has been a long process but one that serves as a model for how new procedures and technologies need to be properly evaluated before being brought into mainstream medical practice. Even so, risks and benefits need to be evaluated for each patient. The currently available studies have been carried out on a highly selected patient population where the fetal findings provided the maximum opportunity for benefit from prenatal closure of the MMC defect. There is the potential that as the surgery becomes more widely available, pressure will be brought to bear to perform surgery in cases where the likelihood for benefit is decreased and yet the risks are not. The only way to duplicate the results of the current studies is to follow the methodology and criteria that were used in the studies. This will mean that not every fetus with an MMC will be a candidate for in utero surgery. The balance of risk to benefit will continue to evolve as further technological advances are evaluated and more follow-up information is obtained. Copyright © 2011 John Wiley & Sons, Ltd.     

Effects of mid-trimester induced abortion on the subsequent pregnancy

The outcome of the pregnancy following (a) a mid-trimester termination of pregnancy (TOP) for fetal neural tube defect (NTD) (77 women=group 1); (b) mid-trimester TOP for fetal Down's syndrome (13 women=group 2); (c) delivery of a baby with NTD (119 women=group 3) was studied. The prenatal fetal loss was relatively high in all groups. In group 1 it was similar to that found in other studies after first trimester TOP, in group 2 it was associated with advanced maternal age and the unexpected finding in group 3 was not attributable to advanced maternal age. It is suggested that a previous NTD per se might increase the risk of fetal loss in the next pregnancy. A previous mid-trimester TOP for NTD was not associated with an increase in premature labour, small for dates babies or congenital abnormality in the next pregnancy, but there was a slight increase in the number of babies weighing less than 2500 g.     

重离子辐照1200V碳化硅二极管漏电退化的缺陷分析

目的研究1200 V碳化硅二极管重离子辐照诱生缺陷对漏电流退化的影响。方法以SiC结势垒肖特基二极管(Junction Barrier Schottky Diode,JBSD)为样品,采用能量为208 MeV,LET=37.3 MeV·cm^2/mg的锗离子进行辐照试验,利用半导体器件分析仪对重离子辐照前后1200 V SiC二极管的电学特性进行测试,利用深能级瞬态谱仪(Deep Level Transient Spectrum,DLTS)进行缺陷分析。结果辐照后,二极管的正向IV特性和CV特性未发生明显变化,反向IV特性退化。DLTS测试结果显示,E0.4能级和Z1/Z2能级基本未发生变化,EH能级有展宽的现象。测试电压VM=-8 V,填充脉冲电压VF=-1 V条件下测得的EH能级浓度比VF=-4 V条件下测得的高。结论分析认为,EH能级的缺陷复杂,推测是两个或多个缺陷能级的叠加(EH4、EH5、EH6、EH7等),此处缺陷的复杂程度与漏电流的退化成正相关,且这些缺陷的所在位置接近SiC外延层的表面。     

A further case with a small supernumerary marker chromosome (sSMC) derived from chromosome 1—evidence for high variability in mosaicism in different tissues of sSMC carriers

A prenatally ascertained case with a de novo small supernumerary marker chromosome (sSMC) derived from chromosome 1 is reported. Due to a fetal heart defect the parents decided in favour of an induced abortion. Postmortem, a molecular cytogenetic study on eleven formalin fixed, paraffin-embedded tissues of the fetus was performed, to further characterize the levels of mosaicism of the sSMC(1). sSMC presence varied between 13 and 62% within different tissues of sSMC carriers. This finding is something common in sSMC carriers and could explain why up to the present no clinical correlations for sSMC mosaicism and clinical outcome in the corresponding carriers could be established. Copyright © 2007 John Wiley & Sons, Ltd.     

Left-sided gastroschisis and bilateral multicystic dysplastic kidneys: a rare combination of anomalies

Left-sided gastroschisis is very rare. We report a case of left-sided gastroschisis associated with bilateral multicystic dysplastic kidneys. This combination of anomalies is unknown. The pathogenesis of gastroschisis is not well understood. It is now viewed as a malformation rather than disruption. The findings in this case support this view. The combination of dysplastic kidneys with ventral body wall defect suggests an early developmental defect. Copyright © 2007 John Wiley & Sons, Ltd.     

Recurrence risk of neural tube defects following a miscarriage

Data from 280 sibships in three published series were used to see if the increased risk of neural tube defect (NTD) associated with having had a miscarriage in the immediately preceding pregnancy was also found in women with a previous affected pregnancy. A statistically significant relative risk of 4.0 (2-tail P=0.0111, Fisher exact test) was found among such women, and this could not be accounted for by the effect of parity or of a history of miscarriage in general. The finding may be useful when counselling patients.     

Prenatal diagnosis of partial trisomy 12q: clinical presentations and outcome

We present a pregnant woman with a fetus prenatally diagnosed as 46, XY,der(4) t(4;12) (q35.1; q21.2). This defect resulted from the unbalanced segregation of a paternal balanced translocation, t(4;12) (q35.1; q21.2). Prenatal ultrasound revealed borderline ventriculomegaly, a thick nuchal fold, pericardial effusion, arthrogryposis, a single umbilical artery, and micropenis. Fluorescence in situ hybridization (FISH) with whole chromosome painting probe and microarray-based comparative genomic hybridization analysis further confirmed chromosomal gain of terminal 12q. The woman had her pregnancy terminated at 20 weeks of gestational age. When compared with previously reported cases, the proband had characteristics common to the phenotypes of partial trisomy 12q, including an abnormal facial appearance and multiple anomalies. Additionally, this case had previously unreported phenotypes, such as arthrogryposis, a single umbilical artery, and a micropenis. Regarding the outcome of partial trisomy 12q, the fetuses carrying trisomies distal to 12q24 have a good chance of extended postnatal survival. In contrast, the cases with trisomies involving a larger amount of 12q likely die prenatally or within a few days after birth. Copyright © 2005 John Wiley & Sons, Ltd.     

Early and severe tricuspid valve dysplasia in a fetus with cardiospondylocarpofacial syndrome due to a variant c.616T>G p.(Tyr206Asp) in MAP3K7

Cardiospondylocarpofacial syndrome (CSCF; MIM#157800) is a rare condition caused by monoallelic variants in the MAP3K7 gene. The characteristic features of CSCF include growth retardation, facial dysmorphism, carpal-tarsal fusion, dorsal spine synostosis, deafness, inner ear malformation, cardiac septal defect and valve dysplasia. We present here a 20-week-old fetus with cardiospondylocarpofacial syndrome arising from a de novo variant c.616T>G p.(Tyr206Asp) in the MAP3K7 (NM_145331.3) gene with early and severe tricuspid valve dysplasia as a prenatal manifestation. Fetal echocardiography revealed tricuspid regurgitation with valve prolapse. Fetus had facial dysmorphism and dilated right atrium and right ventricle with tricuspid valve dysplasia on perinatal evaluation. To the best of our knowledge, this is the first report mentioning the prenatal manifestation of cardiospondylocarpofacial syndrome.     

Prenatal echocardiographic diagnosis of right atrial isomerism

A prenatal diagnosis of right atrial isomerism is often inferred through the recognition of a constellation of cardiac anomalies on the four-chamber view or by the detection of visceral heterotaxy and asplenia. However, the actual occurrence of discordance between the arrangement of the atria and thoracic and abdominal organs makes the identification of the morphology of both atrial appendages the only reliable way to make a final diagnosis of atrial isomerism. Three cases of right atrial isomerism with visceral heterotaxy and a complex cardiac defect, diagnosed in utero by cross-sectional and colour flow Doppler echocardiography, are reported. In all the patients, the right atrial isomerism was associated with an atrioventricular septal defect, a single aortic outlet from the right ventricle, and total anomalous venous return. The diagnosis of right atrial isomerism, always confirmed by neonatal re-evaluation and/or by post-mortem examination, was made through identifying two pyramidal atrial appendages in an echocardiographic transverse plane at the level of the atria and of the origin of the great arteries. This report demonstrates that a final intrauterine diagnosis of atrial isomerism is possible, whatever the visceral situs is.     

Prenatal detection of X-linked ichthyosis by maternal serum screening for down syndrome

Maternal serum unconjugated oestriol (uE3) was measured in 15 375 pregnancies during 2 years of second-trimester risk assessment for Down syndrome using biochemical markers. Very low levels of uE3 (<0·1 MOM) were detected in 22 serum samples (0·14 per cent). Very low uE3 was associated with an adverse outcome in 13 pregnancies including fetal death and miscarriage (N=11), anencephaly (N=1), and Meckel—Gruber syndrome (N=1). Dry scales on the skin appeared in the first year of life in four boys. From dermatological diagnosis, prenatal uE3 levels, and pedigree analysis, it is concluded that at least 5 in approximately 7500 male births in the study population are affected by steroid sulphatase deficiency, which is the biochemical defect in X-linked ichthyosis. Very low uE3 levels in the second trimester are indicative of this disease in pregnancies with normal ultrasound findings.     

First-trimester maternal serum alpha-fetoprotein and human chorionic gonadotropin screening for chromosome defects

The aim of this study was to determine the efficacy of combined maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG) screening in detecting chromosome defects in the first trimester of pregnancy. Sera of 492 women (previously assayed for MSAFP) were analysed for MShCG under code without knowledge of cytogenetic results. Overall, 48 of 492 patients (9·8 per cent) had either an MSAFP multiple of the median ⩽0·5 or an MShCG β/a z ratio multiple of the median ⩽ 0·25, eight of whom had a fetus with a serious chromosome defect. A third of fetuses with Down' s syndrome and 83 per cent with trisomy 18 were detected at a potential‘cost’ of providing chorionic villus sampling or amniocentesis in 8·6 percent of women screened.     

Second trimester maternal serum analytes in triploid pregnancies: correlation with phenotype and sex chromosome complement

Second trimester maternal serum alpha-fetoprotein (MS-AFP), human chorionic gonadotrophin (hCG), unconjugated estiol (uE3), and inhibin-A (INH-A) levels were evaluated in pregnancies complicated by triploidy. In addition to seven new triploid pregnancies, the results for 67 published cases were reviewed. All cases appear to fall into two major groups. First, those identifiable as screen-positive for both Down syndrome and an open neural tube defect (ONTD) with elevated MS-AFP, grossly elevated hCG, low/normal uE3, and probably elevated INH-A. Pregnancies in the second group are identifiable as screen-positive for trisomy 18 with low/normal MS-AFP, and very low hCG, uE3 and INH-A. Triploid pregnancies with high maternal serum hCG nearly always show a placenta with partial mole (25/27 or 93%), a high frequency of ONTDs or ventral wall defects (VWDs) (8/28 or 29%) and have either an XXX or XXY karyotype (observed ratio 6:10, respectively). Low hCG is infrequently associated with a molar placenta (1/11 or 9%), does not appear to be associated with ONTDs or VWDs (0/29 or 0%), and shows an excess of XXX over XXY karyotypes (observed ratio 17:2). There were 16 cases with either a molar placenta, an ONTD or a VWD that received the MS-AFP and hCG tests. All 16 were screen-positive for an ONTD (MS-AFP≥2 multiples of the median). In addition, all 31 cases that received MS-AFP, hCG, uE3 (and where available INH-A) were screen-positive for either Down syndrome or trisomy 18. The findings are discussed in the context of expected differences between digynic and diandric triploidy. It is suggested that the sex chromosome complement in triploidy is an important factor in determining risk for partial mole development and in utero survival. Copyright © 2001 John Wiley & Sons, Ltd.     

Preventing mercury emissions from coal-fired power plants using environmentally preferable coal purchasing practices

Electric utilities in the United States will soon be required under the federal Environmental Protection Agency's Clean Air Mercury Rule to significantly reduce mercury emissions. Coal-fired power plants, including the Lower Colorado River Authority's (LCRA) Fayette Power Project (FPP) have demonstrated that the selective purchasing of coal with low mercury content can result in significant reduction of pollution. This selective activity, commonly known as “green purchasing”, has been applied to the procurement of coal. For example, the use of low-sulfur coal from the Powder River Basin deposits of Wyoming results in the prevention of a significant amount of sulfur dioxide (SO₂) releases to the atmosphere when compared to other sources of coal in the United States. This same philosophy (selective purchasing of coal) can be employed to prevent mercury emissions and substantially reduce mercury removal costs for electric utilities burning coal. Data analysis confirms that low-mercury coal is available and that selective purchasing of low-mercury coal is possible.LCRA has implemented an extensive pollution prevention program and their green purchasing efforts have been expanded to influence coal purchasing choices. Coal purchasing is limited to the Gillette Coal Field from the Powder River Basin (PRB) of Wyoming. Three sets of coal quality data which include LCRA's Coal Quality Database (CQD), a database created from the Information Collection Request (ICR) conducted by the EPA in 1999, and the U.S. Geological Survey (USGS) Coal Quality (COALQUAL) Database were analyzed. Lab accuracy issues were found to have undermined the reliability of certain records in both the CQD and ICR databases, however, both remain valuable resources. The independent sets of coal quality data and technical reports show measurable differences in mercury concentration in coal in the Gillette Coal Field, both geographically (coal mine) and by depth (coal seam). A preliminary cost benefit analysis indicates that substantial cost savings in operating and maintaining mercury control equipment will be realized with low-mercury coal. Currently, low-mercury coal can be purchased without a significant premium.     

Effect of barley chromosome addition on the susceptibility of wheat to feeding by a gall-inducing leafhopper

The maize orange leafhopper Cicadulina bipunctata is distributed widely in tropical and subtropical regions of the Old World and feeds on various Poaceae. The leafhopper is recognized as an important pest of maize in several countries. Adults as well as nymphs of C. bipunctata induce growth stunting and galls characterized by the severe swelling of leaf veins on many cereal crops including wheat, rice, and maize, but do not on barley. To clarify the mechanism of growth stunting and gall induction by C. bipunctata, we used six barley chromosome disomic addition lines of wheat (2H–7H) and investigated the effect of barley (cv. Betzes) chromosome addition on the susceptibility of wheat (cv. Chinese Spring) to feeding by the leafhopper. Feeding by C. bipunctata significantly stunted the growth in 2H, 3H, 4H, and 5H, but did not in 6H and 7H. The degree of gall induction was significantly weaker and severer in 3H and 5H than in Chinese Spring, respectively. These results suggest that barley genes resistant to growth stunting and gall induction exist in 6H and 7H, and 3H, respectively. 5H is considered to be useful for future assays investigating the mechanism of gall induction by this leafhopper because of the high susceptibility to the feeding by C. bipunctata. Significant correlation between the degrees of growth stunting and gall induction was not detected in the six chromosome addition lines and Chinese spring. This implies that these two symptoms are independent phenomena although both are initiated by the feeding of C. bipunctata.     

Prenatal foetal diagnosis of partial trisomy 3q and monosomy 13p due to a maternal balanced rearrangement

The authors describe a case of a male foetus whose ultrasound at 20 weeks' gestation revealed cystic hygroma, cleft lip and ventricular septal defect. Amniotic fluid cytogenetics using GTG banding showed a 46,XY,der(13)t(3;13)(q12;p11.1) rearrangement, and fluorescence in situ hybridization (FISH) delineated the relevant breakpoints. Familial studies identified a maternal balanced translocation involving chromosomes 3 and 13. The post-mortem examination confirmed the prenatal ultrasound findings. Copyright © 2005 John Wiley & Sons, Ltd.     

Isolated sulfite oxidase deficiency: mutation analysis and DNA-based prenatal diagnosis

Isolated sulfite oxidase deficiency is an autosomal recessive, neurological disorder resulting from a defect in SUOX, the gene encoding the enzyme that catalyzes the terminal reaction in the sulfur amino acid degradation pathway. In its classical, severe form, sulfite oxidase deficiency leads to intractable seizures, severe and progressive brain pathology and death at an early age. We report here on clinical features and mutational analysis of the genetic defect in a newborn with sulfite oxidase deficiency. Cultured fibroblasts from this patient exhibited no detectable sulfite oxidase activity, and a unique four base pair deletion was present in the cDNA isolated from the same source. Identification of the same genetic defect in a heterozygous state in each of the parents and the monitoring of subsequent pregnancies in this family by DNA-based prenatal diagnosis are also described. The deletion mutation was identified in a homozygous state in uncultured chorionic villus tissue from the second pregnancy that was subsequently terminated. In the third pregnancy, the presence of sulfite oxidase activity and identification of the mutation in a heterozygous state suggested that the fetus was not affected. This pregnancy resulted in the birth of a normal child. Copyright © 2002 John Wiley & Sons, Ltd.