Twin-to-twin transfusion syndrome--debates on the etiology, natural history and management.
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Arteriovenous Anastomosis↗
Biomedical subjects
B Thilaganathan
Publications and source records attributed to B Thilaganathan.
Sono-endoscopic delineation of the placental vascular equator prior to selective fetoscopic laser ablation in twin-to-twin transfusion syndrome.
OBJECTIVE: To assess the safety and efficacy of a new fetoscopic technique in the management of twin-to-twin transfusion syndrome. STUDY DESIGN: Prospective study of fetoscopic treatment and outcome in 10 pregnancies complicated by severe twin-to-twin transfusion syndrome before 24 weeks' gestation. The sono-endoscopic approach was used to identify the placental vascular equator and photocoagulate any vessels crossing this threshold. RESULTS: The mean gestation at treatment was 20 weeks and 3 days. An average of three to four vessels were ablated during each procedure, with a mean operative time of 24 min (range, 14-31 min). The overall survival rate was 55% (11 of 20) with at least one survivor in 70% (seven of 10) of pregnancies. CONCLUSIONS: Fetoscopic laser ablation is a safe and effective form of treatment in the management of severe twin-to-twin transfusion syndrome. This technique, where vessels crossing the placental vascular equator are identified and photocoagulated fetoscopically, is an alternative to the non-selective and selective methods described previously. This new approach is associated with a shorter operating time, less damage to the normal placental surface vasculature and with survival results that are at least as promising as previously reported techniques.
Endosonography↗
Effectiveness of prenatal chromosomal analysis using multicolor fluorescent in situ hybridisation.
OBJECTIVE: To evaluate the clinical effectiveness of multicolour fluorescent in situ hybridisation (FISH) analysis in routine prenatal diagnosis. DESIGN: Prospective study. SAMPLE: 3,203 amniotic fluid samples. METHODS: Unique DNA (chromosomes 13 and 21) and alpha satellite centromeric-specific (chromosomes X, Y and 18) probes were used in two mixes to permit the simultaneous analysis of several chromosomes. The performance of multicolour FISH and conventional cytogenetic analysis was compared. RESULTS: Conventional cytogenetic analysis identified 111 chromosomal abnormalities, of which 94 were potentially detectable by the FISH technique and 97 would be typically associated with neonatal phenotypic abnormalities. Multicolour FISH analysis detected 84% (93/111) of all chromosome abnormalities and 99% (93/94) of abnormalities where there was a specific probe. The sensitivity of multicolour FISH analysis was 95% (92/97) for chromosomal abnormalities likely to result in an abnormal postnatal outcome. Multiple ultrasound abnormalities were detected in all five cases of clinically relevant chromosomal abnormalities missed by multicolour FISH. FISH results were available within 48 hours and the sample failure rate was 0 x 1% (3/3,202). CONCLUSION: Multicolour FISH analysis is a sensitive and reliable technique for the rapid prenatal diagnosis of chromosomal abnormalities. Examining only five chromosomes allowed 95% of clinically relevant chromosomal abnormalities to be diagnosed correctly. As routine antenatal screening is targeted at the major autosomal trisomies and sex chromosome aneuploidies, multicolour FISH analysis may potentially replace conventional cytogenetic analysis in routine prenatal diagnosis.
Chromosome Aberrations↗
First-trimester nuchal translucency and maternal serum biochemical screening for Down's syndrome: a happy union?
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Chorionic Gonadotropin, beta Subunit, Human↗
First trimester screening for fetal abnormalities.
The debate over the application of nuchal translucency measurement in Down's syndrome screening is still unresolved in some clinicians' minds. Although different authors report a range of sensitivities for Down's syndrome, none question the validity of the association between increased nuchal translucency and fetal aneuploidy. The published literature reveals a lack of congruence over a standard, reproducible method for measuring nuchal translucency. Only with the adoption of uniform methodology, and the establishment of international standards for nuchal translucency measurement, is the true potential of this test likely to be realized. The increasing use of first trimester ultrasound has focused attention on the value of this investigation in confirming fetal viability, estimation of gestational age, and screening for congenital abnormality. This review summarizes the role of ultrasound and maternal serum biochemistry in first trimester screening.
Congenital Abnormalities↗
Isolated fetal echogenic intracardiac foci or golf balls: is karyotyping for Down's syndrome indicated?
OBJECTIVE: To determine the prevalence of isolated echogenic intracardiac foci and the subsequent risk for Down's syndrome at 18-23 weeks in an unselected obstetric population. DESIGN: Prospective study. SETTING: A district general hospital serving a routine obstetric population. PARTICIPANTS: 16,917 pregnant women who underwent a routine ultrasound screening at 18-23 weeks of gestation between November 1994 and August 1998. METHODS: All women were offered screening for Down's syndrome by nuchal translucency or maternal serum biochemistry. The prevalence of isolated echogenic intracardiac foci was determined and the relative risk for Down's syndrome was calculated for different ultrasound findings. RESULTS: The combined sensitivity of age, nuchal translucency and maternal serum biochemistry for Down's syndrome was 84% (27/32). The relative risk for Down's syndrome was 0.17 (95% CI 0.07-0.41) for the women with normal scan findings at 18-23 weeks. The prevalence of isolated echogenic intracardiac foci at 18-23 weeks was 0.9% (144/16,917). None of these pregnancies were affected by Down's syndrome. CONCLUSION: The significance of the association between isolated echogenic intracardiac foci and Down's syndrome is a matter of ongoing debate. The data of this study suggest that in an unselected obstetric population with prior, effective, routine Down's syndrome screening, the association between isolated echogenic intracardiac foci and Down's syndrome is no longer significant.
Adult↗
Increased first trimester nuchal translucency: pregnancy and infant outcomes after routine screening for Down's syndrome in an unselected antenatal population.
Although increased nuchal translucency (NT) has been linked to a wide range of fetal chromosomal abnormalities and genetic syndromes, very few studies have looked at the outcomes of chromosomally normal pregnancies in unselected obstetric populations. This study aims to evaluate the outcomes of pregnancies with nuchal translucency measurements greater than or equal to 4 mm in a low risk obstetric population attending for routine first trimester screening. Women attending for booking scans were routinely offered nuchal translucency measurement as a screening test for Down's syndrome between 10 and 14 weeks gestation. The prevalence of increased nuchal translucency was 0.8% (n = 53). There were 15 (28.3%) chromosomal abnormalities, the commonest of which was Down's syndrome. Of the 38 chromosomally normal pregnancies, seven resulted in intrauterine death, early neonatal death or termination of pregnancy. The remaining 31 cases resulted in livebirths, of which two infants now exhibit developmental delay of unknown aetiology and one has been diagnosed as having Noonan's syndrome. 10 (19%) pregnancies were diagnosed as having major anatomical malformations resulting in fetal or neonatal demise or requiring postnatal surgery. In a routine obstetric population, the finding of an NT measurement greater than or equal to 4 mm is associated with a poor pregnancy outcome in the majority of cases, mainly owing to chromosomal abnormality. This study establishes the need for focused fetal assessment in cases with such first trimester findings.
Adolescent↗
First trimester nuchal translucency: effective routine screening for Down's syndrome.
The objective was to evaluate the effectiveness of 10-14 week nuchal translucency measurement in routine ultrasound screening for Down's syndrome. 11,398 women were scanned at 10-14 weeks of pregnancy for nuchal translucency measurements. The mean maternal age of the screened population was not significantly different from that of the booking population. A 5% screen positive rate was achieved by using a nuchal translucency-derived risk of > or = 1:200. Screening using this nuchal translucency risk would enable the first trimester detection of 16 out of 21 (76%) fetuses with Down's syndrome and 40 out of 49 (81%) aneuploid fetuses. In conclusion, this study demonstrates that first trimester nuchal translucency measurement is an effective method of screening for fetal chromosomal abnormality.
Adolescent↗
Transfer of nucleated maternal cells into fetal circulation during the second trimester of pregnancy.
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DNA↗
Influence of ethnic origin on nuchal translucency screening for Down's syndrome.
OBJECTIVE: To determine the influence of ethnic origin on access to and equity of nuchal translucency screening for Down's syndrome in a multiethnic population. DESIGN: An observational study in a district general hospital with a large multiethnic population. SUBJECTS: 1944 women attending at a hospital antenatal clinic. MAIN OUTCOME MEASURES: First-trimester fetal nuchal translucency measurements at 10-14 weeks in women from different ethnic groups. RESULTS: The racial origin of the screened population was not significantly different from that of the population attending for initial antenatal examination. Multiple regression analysis showed a small but significant difference in nuchal translucency measurement between fetuses of different ethnic origin. CONCLUSION: Nuchal translucency screening can be effectively and equitably delivered to a multiethnic population. Although there are significant differences in nuchal translucency measurement between ethnic groups, these differences are too small to require correction when nuchal translucency is used to screen for Down's syndrome.
Asian People↗
Prolonged pregnancy: evaluating gestation-specific risks of fetal and infant mortality.
OBJECTIVE: To evaluate gestation-specific risks of stillbirth, neonatal and post-neonatal mortality. DESIGN: Retrospective analysis of 171,527 notified births (1989-1991) and subsequent infant survival at one year, from community child health records. SETTING: Notifications from maternity units in the North East Thames Region, London. MAIN OUTCOME MEASURES: The incidence of births, stillbirths, neonatal and post-neonatal deaths at each gestation after 28 completed weeks. Mortality rates per 1000 total or live births and per 1000 ongoing pregnancies at each gestation were calculated. RESULTS: The rates of stillbirth at term (2.3 per 1000 total births) and post-term (1.9 per 1000 total births) were similar. When calculated per 1000 ongoing pregnancies, the rate of stillbirth increased six-fold from 0.35 per 1000 ongoing pregnancies at 37 weeks to 2.12 per 1000 ongoing pregnancies at 43 weeks of gestation. Neonatal and post-neonatal mortality rates fell significantly with advancing gestation, from 151.4 and 31.7 per 1000 live births at 28 weeks, to reach a nadir at 41 weeks of gestation (0.7 and 1.3 per 1000 live births, respectively), increasing thereafter in prolonged gestation to 1.6 and 2.1 per 1000 live births at 43 weeks of gestation. When calculated per 1000 ongoing pregnancies, the overall risk of pregnancy loss (stillbirth + infant mortality) increased eight-fold from 0.7 per 1000 ongoing pregnancies at 37 weeks to 5.8 per 1000 ongoing pregnancies at 43 weeks of gestation. CONCLUSION: The risks of prolonged gestation on pregnancy are better reflected by calculating fetal and infant losses per 1000 ongoing pregnancies. There is a significant increase in the risk of stillbirth, neonatal and post-neonatal mortality in prolonged pregnancy. This study provides accurate data on gestation-specific risks of pregnancy loss, enabling pregnant women and their carers to judge the appropriateness of obstetric intervention.
England↗
Effect of routine screening for Down's syndrome on the significance of isolated fetal hydronephrosis.
OBJECTIVE: To determine the risk of Down's syndrome in fetuses with isolated hydronephrosis at 18-23 weeks in an unselected general population after routine screening for Down's syndrome, using first trimester nuchal translucency measurement and second trimester maternal serum biochemistry. POPULATION: All pregnant women undergoing a routine 18-23 week ultrasound scan, from a population who had been offered screening for Down's syndrome. SETTING: A district general hospital serving a low risk obstetric population. METHODS: Prospective study of all routine 18-23 weeks ultrasound scans. The prevalence of isolated hydronephrosis and Down's syndrome was determined and the relative risk for Down's syndrome was calculated for different ultrasound findings. RESULTS: 10,971 women were scanned at 18-23 weeks during the study period. Down's syndrome was diagnosed in 14 of 20 cases before this stage using first trimester nuchal translucency measurement and second trimester maternal serum biochemistry. Isolated fetal hydronephrosis was diagnosed in 423 pregnancies (3.9%); none of these pregnancies were affected by Down's syndrome. The relative risk for Down's syndrome was 0.18 (95% CI 0.06-0.53) for women with a normal scan (n = 9983). When multiple ultrasound markers were found (n = 565), the relative risk for Down's syndrome was 2.00 (95% CI 0.18-22.10) and 9.00 (95% CI 1.14-71.30) for all other aneuploidies. CONCLUSION: The finding of isolated fetal hydronephrosis does not significantly increase the age-related risk for Down's syndrome. The presence of multiple ultrasound markers is associated with an increased risk of aneuploidies other than Down's syndiome. These findings are explained by the reduced prevalence of Down's syndrome as a result of prior screening and diagnosis of this condition.
Adult↗
Effect of first-trimester nuchal translucency on second-trimester maternal serum biochemical screening for Down's syndrome.
We evaluated the effectiveness of 10-14 week nuchal translucency measurement in routine ultrasound screening for Down's syndrome, and its effect on the sensitivity of subsequent maternal serum biochemistry. This was an observational study, in which all women attending for antenatal care at a district general hospital were routinely offered a first-trimester nuchal translucency scan and second-trimester quadruple maternal serum biochemistry as screening tests for Down's syndrome. The main outcome measures were abnormal fetal karyotype and the performance of screening tests. A total of 3604 women were scanned in the first trimester of pregnancy. Excluding the cases that did not fit the entry criteria (n = 344, 9.6%) and in which nuchal translucency measurements were not possible (n = 340, 9.4%), a total of 2920 women were screened. A nuchal translucency-derived risk of 1:200 for an aneuploid pregnancy resulted in a 5% (n = 147) screen-positive rate. Screening using this risk enabled the first-trimester detection of five of seven (71%) fetuses with trisomy 21 and 14 of 18 (78%) aneuploid fetuses. Second-trimester maternal serum biochemistry testing was performed in 1904 of the women who had nuchal translucency screening, with a screen-positive rate of 7.5% (n = 143). Only one extra case of Down's syndrome would have been detected by maternal serum biochemistry testing if nuchal translucency screening had been implemented at a risk level of 1:300. This study demonstrates that first-trimester nuchal translucency measurement is effective in routine screening for fetal chromosomal abnormality. Furthermore, the implementation of a nuchal translucency screening program will significantly reduce the positive predictive value of second-trimester maternal serum biochemistry testing.
Adult↗
Two-way cell traffic between mother and fetus: biologic and clinical implications.
The bilateral trafficking of nucleated cells between the fetus and the mother was studied using polymerase chain reaction (PCR)-based systems sensitive enough to detect 1 target cell in 100,000 background cells. Sixty-six mother-baby pairs were recruited; maternal and cord blood samples were collected at delivery for DNA extraction. Cell trafficking was studied in informative cases using PCR-genotyping of polymorphic regions in the beta-globin cluster, the glutathione S-transferase M1 locus and the angiotensin converting enzyme gene. In addition, Y-PCR was also used in conjunction with these systems for the detection of fetal cells in maternal circulation. Fetal cells were detected in maternal peripheral blood in 26 of 51 cases whereas maternal cells were detected in 16 of 38 fetal umbilical cord blood samples. The proportion of umbilical samples with detectable maternal sequences was much higher than previously reported. In the 28 cases informative for both mother and baby, there was no obvious correlation between the cell traffic from mother to baby as compared to that from baby to mother. These findings may have implications for the use of cord blood for bone marrow transplantation, the vertical transmission of infectious agents, and the physiology of the feto-maternal relationship.
Blood Cells↗
Nuchal translucency: a marker for the antenatal diagnosis of aortic coarctation.
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Aortic Coarctation↗
Blood transferrin receptor expression in chromosomally abnormal fetuses.
In a cross-sectional study of 13 chromosomally abnormal fetuses, umbilical venous blood was obtained by cordocentesis at 17-32 weeks' gestation. Fetal blood transferrin receptor (CD71) expression (mean = 79.8 per cent, range = 60-98 per cent) and nucleated red cell count (mean = 10.4 x 10(9) per 1, range = 1.0-25.0 x 10(9) per 1) were significantly higher than the appropriate normal mean for gestation (z = 3.92, P < 0.0001 and z = 3.69, P < 0.001, respectively). These haematological changes in chromosomally abnormal fetuses would facilitate their prenatal diagnosis by analysis of fetal nucleated red blood cells isolated from the maternal circulation on the basis of CD71 expression.
Chromosome Aberrations↗
Neutrophil and monocyte beta 2-integrin expression in trisomic fetuses.
Flow cytometry was used to measure neutrophil and monocyte beta 2-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 beta 2-integrin expression between normal and aneuploid fetuses. These findings demonstrate that in trisomies 21 and 18, alteration in beta 2-integrin expression is unlikely to contribute to the pathogenesis of immunological deficiencies that have been observed in these aneuploidies both prenatally and postnatally.
Aneuploidy↗
Maternal platelet size as a marker for fetal trisomies 18 and 13.
Maternal and fetal platelet size and glycoprotein expression were measured in 14 pregnancies complicated by fetal aneuploidy between 20 and 24 weeks' gestation. Flow cytometry was used to determine platelet size and surface glycoprotein Ib (GPIb) and GPIIIa expression both before and after stimulation with adenosine diphosphate (ADP). The data were compared with results obtained from 35 normal paired maternal and fetal controls. In fetuses affected with trisomies 18 and 13, but not trisomy 21, the maternal and fetal platelet sizes were significantly higher than those of the normal controls. Furthermore, the increase in fetal platelet size was significantly associated with the increase in maternal platelet size. Increase in maternal platelet size may be of potential value as a marker for fetal trisomies 18 and 13.
Blood Platelets↗