Cardiac blood flow studies in fetuses with haemoglobin bart's disease

Blood flow across the atrioventricular valves and outflow tracts was measured in 55 normal fetuses and 32 fetuses with haemoglobin (Hb) Bart's disease between 18 and 26 weeks of gestation. The mean velocities remained unchanged in both normal and affected fetuses over the gestations studied. The volume flow across both atrioventricular valves and outflow tracts increased as the gestation advanced in both normal and affected fetuses, but was significantly higher in affected than in normal fetuses. The same magnitude of increased flow was found in both hydropic and non-hydropic fetuses with Hb Bart's disease. These findings suggest that fetuses with severe and long-standing anaemia have a remarkable cardiac compensatory mechanism for the maintenance of tissue oxygenation. In response to anaemia and circulatory loading, the cardiac chambers and outflow tracts enlarge proportionately up to twice the normal values. Because of this response and the operation of the Frank-Starling mechanism, the heart is able to maintain a normal mean velocity of propulsion and the net output is increased to two to three times that in normal fetuses. Hydropic changes in these anaemic fetuses appear unrelated to cardiac failure as cardiac failure is not observed at the time that hydropic changes develop.     

Tertiary centre referral of small-for-gestational age pregnancies: A 10-year retrospective analysis

Between 1981 and 1991, 461 pregnant women between 15 and 40 weeks of gestation (mean 30 weeks) with completed follow-up were referred to our centre for prenatal diagnosis because of a small-for-gestational age (SGA) fetus or combined SGA and structural abnormality. The referral diagnosis was based either on biparietal diameter measurements or on measurement of the upper-abdominal circumference. SGA in our centre was defined as a fetal upper-abdominal circumference below the tenth centile. SGA was confirmed by ultrasound in 75 per cent of the fetuses, whilst combined SGA and fetal structural abnormality was substantiated in only 16 per cent of the fetuses. However, in our centre structural abnormality was detected in 34 fetuses who were referred because of SGA alone. Nearly half of the structurally normal SGA fetuses displayed a normal head-to-abdomen (H/A), ratio, whereas an increased H/A ratio was found in 13/15 fetuses with an abnormal karyotype. An abnormal karyotype was present in 20 fetuses, which is 7 per cent of the total SGA population. Nearly 50 per cent represented triploidy associated with oligohydramnios. SGA was confirmed by a birth weight below the tenth centile in 89 per cent, below the fifth centile in 77 per cent, and below the 2·3rd centile in 55 per cent of infants. Structural abnormality was confirmed in 65 per cent of infants, whereas in 19 per cent of infants the abnormality was missed or a misclassification was made. Perinatal mortality was 31 per cent for all SGA fetuses, 27 per cent for SGA fetuses without anomalies, and 64 per cent for SGA fetuses with structural abnormality.     

Turner syndrome-omphalocele association: Incidence,karyotype, phenotype and fetal outcome

Objective

Omphalocele is known to be associated with genetic anomalies like trisomy 13, 18 and Beckwith–Wiedemann syndrome, but not with Turner syndrome (TS). Our aim was to assess the incidence of omphalocele in fetuses with TS, the phenotype of this association with other anomalies, their karyotype, and the fetal outcomes.

Method

Retrospective multicenter study of fetuses with confirmed diagnosis of TS. Data were extracted from a detailed questionnaire sent to specialists in prenatal ultrasound.

Results

680 fetuses with TS were included in this analysis. Incidence of small omphalocele in fetuses diagnosed ≥12 weeks was 3.1%. Including fetuses diagnosed before 12 weeks, it was 5.1%. 97.1% (34/35) of the affected fetuses had one or more associated anomalies including increased nuchal translucency (≥3 mm) and/or cystic hygroma (94.3%), hydrops/skin edema (71.1%), and cardiac anomalies (40%). The karyotype was 45,X in all fetuses. Fetal outcomes were poor with only 1 fetus born alive.

Conclusion

TS with 45,X karyotype but not with X chromosome variants is associated with small omphalocele. Most of these fetuses have associated anomalies and a poor prognosis. Our data suggest an association of TS with omphalocele, which is evident from the first trimester.     

Minor sonographic signs of trisomy 21 at 15–20 weeks' gestation in fetuses born without malformations: a prospective study

A prospective study was performed on 2119 pregnancies that underwent genetic amniocentesis. Indications for amniocentesis were either maternal age (⩾35) or triple-test results (risk⩾1/380). The study covered a 36-month period and assessed the prevalence of minor ultrasound markers both in fetuses with Down syndrome and normal control fetuses at 15–19 week' gestation. Only fetuses with normal karyotype or trisomy 21 were considered. Six minor sonographic markers were considered: nuchal thickness, pyelectasia, femur observed/expected and humerus observed/expected ratios, bowel echogenicity, and choroid plexus cysts. One or more ultrasound soft markers were present in 23 out of 33 fetuses with Down syndrome (70%) and in 572 out of 2069 normal fetuses (28%). Copyright © 2001 John Wiley & Sons, Ltd.     

Evaluation of prenatal diagnosis by a registry of congenital anomalies

Prenatal diagnosis performed by fetal karyotype and ultrasound scan is now a routine part of antenatal care in many countries. How many fetal anomalies are actually detected by these procedures? We have used our registry of congenital malformations to answer this question. In our region, prenatal diagnosis was performed in 23.1 per cent of fetuses with a chromosomal aberration and in 20.1 per cent of fetuses with non-chromosomal anomalies. Only 6.9 per cent of the pregnancies with fetuses with non-chromosomal anomalies were terminated. The sensitivity of prenatal diagnosis by ultrasonographic examination was much lower for isolated malformations (fetuses with only one anomaly) than for multiple malformed children, 15.3 and 48.3 per cent respectively, chromosomal anomalies excluded.     

Prenatal karyotyping in malformed fetuses

Experience with prenatal karyotyping of 237 fetuses with sonographic evidence of malformation is reported. Abnormal karyotype was found in 40 cases (16-8 per cent): chromosomal aberrations were found in 19 of the 178 fetuses with an isolated structural anomaly (10-6 per cent) and in 21 of the 59 fetuses with multiple malformations (35-6 per cent). Detailed cytogenetic and morphological information concerning fetuses affected by omphalocele, duodenal atresia, hydrocephalus, multicystic kidney, unilateral hydronephrosis and cystic hygroma is reported. The need for a very careful ultrasound evaluation of fetal anatomy in these pregnancies is stressed, as the risk of a chromosomal anomaly depends mainly on the existence of more than one ultrasonically diagnosed structural defect.     

Karyotype abnormalities in fetuses diagnosed as abnormal on ultrasound before 20 weeks' gestational age

This study examined rates of karyotype abnormalities in fetuses diagnosed by ultrasound as abnormal before 20 weeks' gestational age and which prompted a follow-up amniocentesis or chorionic villus sampling. Those diagnosed before 20 weeks were compared with those diagnosed at or after 20 weeks. A retrospective study identified ultrasonographically abnormal fetuses in whom karyotyping had been undertaken, 306 fetuses before 20 weeks' gestational age and 241 after. Isolated malformations before 20 weeks had, on average, an 18 per cent risk of karyotype abnormality, compared with 20 per cent later. Specific rates were calculated; for example, heart abnormality was associated with karyotype abnormality in 7 per cent of cases before 20 weeks and in 14 per cent later. Multiple malformations and karyotype abnormalities were found together in 28 per cent of fetuses prior to 20 weeks and in 33 per cent of the older fetuses. Specific associations included nuchal oedema and trisomy 21 in 21 per cent of fetuses before 20 weeks. No karyotype abnormalities were found in fetuses diagnosed with choroid plexus cysts. An overview of trisomies in Victoria, in 1991, showed that 50 per cent of trisomy 18, 42 per cent of trisomy 13, and 9·5 per cent of trisomy 21 cases were identified by ultrasound in women less than 37 years of age. Another 28·6 per cent of trisomy 21 fetuses were detected in women of advanced maternal age who underwent amniocentesis or chorionic villus sampling, making a total of 38·1 per cent of trisomy 21 that were detected prenatally. The importance of early karyotyping specifically relates to the ongoing management of the pregnancy if the chromosomes are normal, and facilitates decision-making regarding termination of pregnancy if the chromosomes are abnormal.     

Fetal behaviour in growth retardation: Its relationship to fetal blood flow

The fetal behaviour of asymmetrical growth retarded fetuses was compared with that of a control group of healthy fetuses. Fetuses underwent simultaneous cardiotocographic and echographic examinations for two consecutive hours at 36–38 weeks of gestation. The distribution of gross fetal body movements, fetal breathing movements and fetal eye movements was analysed during the different fetal heart rate patterns. Furthermore, the incidence and organization of fetal behavioural states was investigated. The degree of vascular peripheral resistance was also evaluated by means of pulsed doppler ultrasonic equipmznt. Growth retarded fetuses were divided into two groups on the basis of the presence or absence of end diastolic flow in the fetal thoracic descending aorta. Growth retarded fetuses showed a delay in the integration of behavioural patterns and a lower coincidence of behavioural states. These findings are particularly evident in the fetuses with a severe increase of peripheral vascular resistance (absence of end diastolic flow in descending aorta). Thus, we suggest that a delay in central nervous system development is present in asymmetrical growth retarded fetuses and that there is a possible relationship of this delay to the degree of peripheral vascular resistance.     

Uniparental disomy in fetuses diagnosed with balanced Robertsonian translocations: risk estimate

Forty-two fetuses with non-homologous Robertsonian translocations were analyzed for uniparental disomy (UPD). One fetus with a de novo translocation t(13q;14q) had maternal isodisomy of chromosome 14. In a summary of the published data (including the present study), 315 cases were analyzed for UPD after prenatal diagnosis of balanced Robertsonian translocations, of these two fetuses had UPD, giving a risk estimate of 0.65% (CI 0.2–2.3). This risk justifies the recommendation of UPD analysis in fetuses diagnosed prenatally with Robertsonian translocations, with the emphasis on the chromosomes known to contain imprinted genes, such as 14 and 15. We also discuss the possibility of UPD in offspring of Robertsonian translocation carriers with normal karyotype. Based on the risk for UPD in fetuses with Robertsonian translocation we suggest to test these fetuses for UPD and to do so on amniocytes rather than chorionic villi when the risk for unbalanced karyotype is ∼1%, comparable to the risk for UPD. Copyright © 2002 John Wiley & Sons, Ltd.     

Quantitative evaluation of collagen type VI and SOD gene expression in the nuchal skin of human fetuses with trisomy 21

Objective To investigate the involvement of the genes encoding for COL6A1, COLA2 and super-oxide dismutase (SOD) in the mechanism for the retention of subcutaneous fluid in fetuses with trisomy 21. Methods During a 7-month period (November 2004–May 2005), human fetal skin from the nuchal region was obtained from euploid fetuses and from fetuses with trisomy 21 following abortions and terminations of pregnancy. Cell cultures were performed from nuchal skin. Quantification of COL6A1, COL6A2, COL6A3 and SOD mRNAs were performed using real-time quantitative RT-PCR. Results Twelve fetuses were studied between 13–15 and 19–20 weeks of gestation including 7 cases of trisomy 21. A significant overexpression of genes of interest was demonstrated in trisomy 21 fetuses when compared with euploid fetuses, in the first and in the second trimester of pregnancy (p < 0.0001). Conclusion This study demonstrates a homogeneous overexpression of the genes encoding for α1 and α2 chains of Collagen type VI, and SOD in nuchal skin of human trisomy 21 fetuses. Persistence of this overexpression in the second trimester of pregnancy, despite the absence of an enlarged nuchal translucency (NT), may characterize some compensatory mechanisms. Copyright © 2007 John Wiley & Sons, Ltd.     

Karyotype,phenotype and parental origin in 19 cases of triploidy

The parental origin of triploidy in 19 cases was examined by inheritance of DNA microsatellites and by methylation patterns of SNRPN or PW71 (where parents' blood was unavailable). The fetal and placental morphology on these cases was reviewed. The phenotype of the fetuses with non-mosaic triploidy was assessed in relation to the two types described by McFadden and Kalousek. Of the diandric fetuses three of the six showed mild-to-moderate symmetrical growth retardation and the other three had growth characteristics in accordance with their gestational ages. This study would suggest the fetal triploid ‘Type 1’ definition be modified to ‘well grown to moderate symmetrical IUGR’ to allow for such variation. In the digynic fetuses (McFadden/Kalousek Type 2) there were poor growth characteristics with IUGR being more severe and asymmetrical. The diandric fetuses were as common as digynic fetuses in this series. The ratio of diandric to digynic specimens was 11:8 but if only fetal specimens (not embryos or mosaic children) were included the ratio was 6:5. Many diandric conceptions end as partial moles but later in gestation diandric fetuses may be well grown. It is proposed that there may be a survival barrier for diandric fetuses early in gestation (possibly based on the proportion of vascularised placental villi), although once this is passed the diandric fetuses are comparatively more viable and better grown than digynic fetuses. In the XXY triploid fetuses, 5/6 had hypoplastic or ambiguous external genitalia (two were recorded as of female phenotype) as has been reported previously. In these, the gonadal histology was testicular in all the diandrics but in the single digynic XXY case, sex reversal was complete with normal uterus and Fallopian tubes and the gonads were histologically ovaries. Two triploid/diploid mosaics were proven to be due to digyny. The probable cause is delayed incorporation of the second polar body into a blastomere and there was evidence of identical alleles from the same sperm being present in both diploid and triploid cells. In one of these triploid/diploid mosaics in which there was a termination of pregnancy (TOP) after prenatal karyotyping the diploid cell line had trisomy 16 which was not evident in the triploid line. This trisomy was probably of post-zygotic origin and we suggest the fetus was rescued by the prominence of the triploid line. Copyright © 2001 John Wiley & Sons, Ltd.     

The efficacy of flecainide versus digoxin in the management of fetal supraventricular tachycardia

Fetal supraventricular tachycardia (SVT) can be successfully treated transplacentally, but in cases where fetal hydrops develops there is considerable morbidity and mortality. The present study was carried out to establish whether the introduction of flecainide altered obstetric management and fetal outcome. A retrospective analysis took place of 51 singleton pregnancies which were referred to the division of prenatal diagnosis because of fetal tachycardia between 1982 and 1993. SVT was documented in 50 out of 51 fetuses, one of which displayed a combination of extensive rhabdomyomas and severe hydrops and died shortly after referral. In the other fetus ventricular tachycardia was diagnosed. Of the remaining 49 fetuses, 14 did not receive any prenatal treatment, but nine needed postnatal treatment. Transplacental treatment of SVT took place in 35 fetuses, of which 22 presented without hydrops and 13 with hydrops. These subsets differed significantly with respect to restoration of normal sinus rhythm (73% vs. 30%; p<0.001) and mortality (0% vs. 46%; p<0.001). Digoxin was effective in restoring sinus rhythm in 55 per cent of the non-hydropic fetuses but in only eight per cent of the hydropic fetuses. Flecainide was effective in restoring sinus rhythm in all non-hydropic fetuses where digoxin treatment failed, and in 43 per cent of hydropic fetuses. Administration of flecainide resulted in a significantly reduced mortality (p<0.001) compared with digoxin treatment. No adverse effects were seen. Postnatal anti-arrhythmic treatment was necessary in 23 infants. Treatment could be withdrawn within one year in all cases but one.     

Nuchal translucency thickness and outcome in chromosome translocation diagnosed in the first trimester

In order to determine the significance of nuchal translucency thickness on the subsequent natural history of first-trimester fetuses with a chromosome translocation, seven consecutive cases diagnosed between 11 and 13 weeks of gestation were reviewed. Nuchal translucency measurements were successfully obtained before chorionic villus sampling (CVS) in all cases. Three fetuses had an unbalanced translocation and all were associated with increased nuchal translucency and multiple anomalies at the detailed second-trimester scan. There were no survivors in this group. The remaining four fetuses had a balanced translocation; all had normal nuchal translucency thickness and no structural anomalies were detected in the second trimester. Three of these fetuses were born at ≥35 weeks of gestation and were phenotypically normal. However, an unexpected single fetal demise occurred in a dichorionic twin pregnancy at 28 weeks of gestation. It is concluded that nuchal translucency measurements provide important prognostic information on pregnancy outcome in first-trimester fetuses with a chromosome translocation. In parents with a known balanced translocation, the detection of increased nuchal translucency at 11–14 weeks of gestation is associated with unbalanced translocations, structural anomalies and poor pregnancy outcome. Copyright © 2001 John Wiley & Sons, Ltd.     

The causes and natural history of fetal ascites

The purpose of this study was to examine the natural history and differential diagnosis of ultrasound-detected, isolated fetal ascites. Retrospective review of our patient data base, from 1989 to 1993, revealed 18 patients with fetal ascites diagnosed sonographically. Fetuses presenting with generalized hydrops were excluded. One of the 18 fetuses with ascites had a chromosomal abnormality (trisomy 21), four fetuses had intrauterine infections, seven had gastrointestinal processes, two had genitourinary tract abnormalities, and four were labelled as ‘idiopathic’ (all four resulting in normal neonates). Seventeen of 18 fetuses survived; there was one fetal demise secondary to active syphilis. One fetus with parvovirus infection required intrauterine transfusion and did well. Two infants are developmentally retarded, including one with trisomy 21 and one with microcephaly secondary to cytomegalovirus infection. Fourteen of 18 fetuses had documented in-utero resolution of the ascites. Eleven of the 18 were associated with polyhydramnios sometime during fetal life. None of the fetuses developed hydrops. In conclusion, fetal ascites can result from many different aetiologies, including gastrointestinal and genitourinary anomalies. Chromosomal abnormalities and viral aetiologies must also be considered. Fetuses who have isolated ascites can have a good outcome with resolution of the ascites antenatally.     

Intrauterine growth retardation and fetal transverse cerebellar diameter

In 103 small-for-gestational age (SGA) fetuses, the transverse cerebellar diameter (TCD), abdominal circumference (AC), head circumference (HC), and femur length (FL) were measured and their ratios calculated. In addition, umbilical venous blood samples were obtained by cordocentesis for measurements of fetal blood pH and erythroblast count. Compared with the AC, HC, and FL, the TCD was relatively mildly reduced. However, in the 28 fetuses with TCD >2 SDs (standard deviations) below the normal mean, the degrees of growth retardation, acidaemia, and erythroblastosis were more severe, and the incidence of perinatal death was higher than in the group with a normal sized TCD. Although in the group with TCD >2 SDs below the normal mean the TCD/AC ratio was increased, in the most severely growth-retarded fetuses this ratio was usually within the normal range. Thus, in intrauterine growth retardation (IUGR), cerebellar size is reduced in proportion to the severity of the disease and therefore the TCD cannot be used to obtain reliable information on the gestational age of small fetuses and the TCD/AC ratio does not provide reliable information as to whether or not fetuses are growth-retarded.     

First-trimester diagnosis of hunter syndrome: Very low iduronate sulphatase activity in chorionic villi from a heterozygous female fetus

Iduronate sulphatase activity was determined in uncultured chorionic villi from four fetuses at risk for Hunter syndrome. AH fetuses were shown to be female by chromosome analysis. Biopsy material from three fetuses showed iduronate sulphatase activity within normal limits whilst the fourth fetus showed activity reduced to 7 per cent of our control mean. The importance of fetal sexing in prenatal diagnosis of this condition is emphasized as female carrier fetuses may show iduronate sulphatase activity reduced to levels observed in affected males.     

弘文重教十余年的《文教资料简报》

创刊于1972年12月的《文教资料简报》是由南京师范学院(1984年易名为南京师范大学)内部编印的资料性月刊,主要目的是为文科教研服务。本文回顾该刊从创办至拥有"统一刊号"、从非正式出版物至成为正式出版物的历史沿革,具体观照该刊的编辑理念,总结该刊的内容特色、文献价值及经验启示。     

Sonographic diagnosis of fetal congenital cataracts

Five fetuses with congenital cataracts diagnosed in utero by ultrasound are reported. The fetuses, who were between 14 and 27 weeks' gestation, also had other severe malformations. The sonographic features of the cataracts are presented.     

Blood chemistry of human fetuses in the second and third trimesters

Six biochemical parameters and four enzyme activities were determined from the serum of 76 healthy and 56 pathological human fetuses between the 20th and 38th week of pregnancy. In the normal fetuses studied within that period, creatinine, immunoglobulin M, lactate dehydrogenase, and gamma-glutamyltransferase increased; haemoglobin F and glucose progressively decreased; and alkaline phosphatase was at a peak around the 26th week; cholesterol and triglycerides were always low. The same parameters were also measured in some of the pathological fetuses and compared with their normal counterparts.     

Neutrophil and monocyte β2-integrin expression in trisomic fetuses

Flow cytometry was used to measure neutrophil and monocyte β2-integrin expression in fetuses with trisomy 18 (n=7) and trisomy 21 (n=7) at 20–25 weeks' gestation. The values were compared with those of 112 chromosomally normal fetuses. There were no significant differences in β2-integrin expression between normal and aneuploid fetuses. These findings demonstrate that in trisomies 21 and 18, alteration in β2-integrin expression is unlikely to contribute to the pathogenesis of immunological deficiencies that have been observed in these aneuploidies both prenatally and postnatally.