-
Ultrasound in Obstetrics & Gynecology :... Nov 2020Celocentesis is an invasive technique that can provide prenatal diagnosis of single-gene disorders, from as early as 7 weeks' gestation. The objective of this study...
OBJECTIVE
Celocentesis is an invasive technique that can provide prenatal diagnosis of single-gene disorders, from as early as 7 weeks' gestation. The objective of this study was to examine the safety of celocentesis.
METHODS
In this prospective study, celocentesis was performed for prenatal diagnosis of hemoglobinopathy in 402 singleton pregnancies in which both parents were carriers of β-thalassemia or sickle cell disease trait. We assessed procedure-related maternal discomfort or pain, success of sampling and obtaining results, pregnancy outcome and postnatal follow-up.
RESULTS
First, celocentesis was carried out at a median gestational age of 8.6 (range, 6.9-9.9) weeks and celomic fluid was successfully aspirated in 99.8% of cases. Second, 67% of women had no or only mild discomfort, 18% had moderate discomfort, 12% had mild-to-moderate pain and 3% had severe pain. Third, prenatal diagnosis from analysis of the celomic fluid was successful in 93.8% cases, and in the last 121 cases, it was always successful. Fourth, in all cases of successful sampling and analysis of celomic fluid, the diagnosis was concordant with results obtained from additional prenatal or postnatal testing. Fifth, in addition to diagnosis of hemoglobinopathy, quantitative fluorescence polymerase chain reaction analysis, which was performed to evaluate maternal contamination using several markers for chromosomes X, Y, 21, 18 and 13, led to the accurate diagnosis of chromosomal aneuploidy. Sixth, in all cases of an affected fetus diagnosed by celocentesis in which the parents chose termination of pregnancy, this was carried out < 10 weeks' gestation. Seventh, in 97.1% (298/307) of the continuing pregnancies there was live birth, in seven (2.3%) there was miscarriage and in two (0.7%) there was loss to follow-up. Eighth, fetal abnormalities were diagnosed in three (1%) cases, including unilateral transverse amputation of the forearm, unilateral moderate hydronephrosis and small-bowel duplication. All neonates were examined by a pediatrician and were found to be phenotypically normal, except for the three cases with a prenatally diagnosed defect.
CONCLUSIONS
Celocentesis can be used for early prenatal diagnosis of genetic abnormalities, and the procedure-related risk of pregnancy complications appears to be low. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Abortion, Eugenic; Adult; Early Diagnosis; Female; Genetic Testing; Gestational Age; Hemoglobinopathies; Humans; Infant, Newborn; Paracentesis; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Pregnancy Trimester, First; Prenatal Diagnosis; Prospective Studies; Ultrasonography, Prenatal
PubMed: 32339311
DOI: 10.1002/uog.22059 -
European Journal of Medical Genetics Jan 2023The diagnosis of prenatal microcephaly, as well as the possibility of underlining a genetic cause, is becoming more frequent thanks to advances in prenatal imaging and... (Review)
Review
The diagnosis of prenatal microcephaly, as well as the possibility of underlining a genetic cause, is becoming more frequent thanks to advances in prenatal imaging and parallel massive sequencing. One case of primary microcephaly in three sibs demonstrates how complementary diagnostic exams can help to diagnose and establish the etiology.
Topics: Pregnancy; Female; Humans; Microcephaly; Ultrasonography, Prenatal; Fetus; Neuroimaging; Genomics; Prenatal Diagnosis
PubMed: 36374791
DOI: 10.1016/j.ejmg.2022.104652 -
Prenatal Diagnosis Jun 2022Prenatal exome sequencing (ES) for monogenic disorders in fetuses with structural anomalies increases diagnostic yield. In England there is a national trio ES service...
BACKGROUND
Prenatal exome sequencing (ES) for monogenic disorders in fetuses with structural anomalies increases diagnostic yield. In England there is a national trio ES service delivered from two laboratories. To minimise incidental findings and reduce the number of variants investigated, analysis uses a panel of 1205 genes where pathogenic variants may cause abnormalities presenting prenatally. Here we review our laboratory's early experience developing and delivering ES to identify challenges in interpretation and reporting and inform service development.
METHODS
A retrospective laboratory records review from 01.04.2020 to 31.05.2021.
RESULTS
Twenty-four of 116 completed cases were identified as challenging including 13 resulting in difficulties in analysis and reporting, nine where trio inheritance filtering would have missed the diagnosis, and two with no prenatal diagnosis; one due to inadequate pipeline sensitivity, the other because the gene was not on the panel. Two cases with copy number variants identified were not detectable by microarray.
CONCLUSIONS
Variant interpretation requires close communication between referring clinicians, with occasional additional examination of the fetus or parents and communication of evolving phenotypes. Inheritance filtering misses ∼5% of diagnoses. Panel analysis reduces but does not exclude incidental findings. Regular review of published literature is required to identify new reports that may aid classification.
Topics: Exome; Female; Fetus; Humans; Pregnancy; Prenatal Diagnosis; Retrospective Studies; Ultrasonography, Prenatal; Exome Sequencing
PubMed: 35506549
DOI: 10.1002/pd.6165 -
Prenatal Diagnosis Jun 2024
Topics: Humans; Pregnancy; Female; Cardiology; Fetal Heart; Heart Defects, Congenital; Fetal Diseases; Prenatal Diagnosis
PubMed: 38801221
DOI: 10.1002/pd.6613 -
American Family Physician Dec 2022
Topics: Pregnancy; Female; Humans; Noninvasive Prenatal Testing; Prenatal Diagnosis; Chromosome Disorders
PubMed: 36521455
DOI: No ID Found -
Echocardiography (Mount Kisco, N.Y.) Oct 2022The objective of this study is to examine the application value of two-dimensional (2D) and high-definition live (HDlive) flow combined with spatiotemporal image...
OBJECTIVES
The objective of this study is to examine the application value of two-dimensional (2D) and high-definition live (HDlive) flow combined with spatiotemporal image correlation (STIC) in diagnosing fetal total anomalous pulmonary venous connection (TAPVC).
METHODS
Seventeen cases of fetal TAPVC were diagnosed using 2D and HDlive Flow combined with STIC. These cases were then retrospectively analyzed to examine the value of using 2D and HDlive Flow combined with STIC in the diagnosis of TAPVC.
RESULTS
2D and HDlive Flow combined with STIC detected 13 cases of supracardiac TAPVC (two isolated cases, seven cases with right atrial isomerism (RAI), four cases with other complex malformations), one case of isolated intra-cardiac TAPVC, and three cases of cardiac TAPVC (two isolated cases and one case with complex congenital heart anomaly). Small left atrium (LA), the absence of PVs drainage into the LA and the increased retroatrial distance between LA and the descending aorta (DAo) were significant signs that should raise the suspicion of fetal TAPVC. HDlive Flow combined with STIC can dynamically display the TAPVC which may assit the prenatal diagnosis of TAPVC.
CONCLUSION
2D and HDlive Flow combined with STIC can assit the diagnosis of fetal TAPVC abnormalities and has important clinical value.
Topics: Female; Humans; Pregnancy; Prenatal Diagnosis; Retrospective Studies; Scimitar Syndrome; Ultrasonography, Prenatal
PubMed: 36100867
DOI: 10.1111/echo.15429 -
European Journal of Obstetrics,... Mar 2022
Topics: Aorta; Aortic Coarctation; Female; Humans; Pregnancy; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 35012766
DOI: 10.1016/j.ejogrb.2021.12.035 -
Journal of Obstetrics and Gynaecology :... Jul 2022Cockayne's syndrome (CS) is a rare autosomal recessive multisystem disease characterised by early severe progression of symptoms. This study reports the feasibility of...
Cockayne's syndrome (CS) is a rare autosomal recessive multisystem disease characterised by early severe progression of symptoms. This study reports the feasibility of earlier prenatal diagnosis of CS by coelocentesis at 8 weeks of gestation respect to amniocentesis or villocentesis. Three couples at risk for CS asked to perform prenatal diagnosis by coelocentesis. Coelomic fluid was aspired from coelomic cavity in four singleton pregnancy at 8 weeks of gestation and 40 foetal cells were recovered by micromanipulator. Maternal DNA contamination was evaluated by quantitative fluorescent PCR (QF-PCR) and target regions of foetal DNA containing parental mutations of ERCC6 gene were amplified and sequenced. In all these cases, molecular analysis was possible. One foetus resulted affected of CS and the diagnosis was confirmed on placental tissue after voluntary abortion. In three cases, foetuses resulted carrier of a parental mutation and the results were confirmed after the birth. This study suggests that reliable prenatal diagnosis of CS could be performed using foetal cells present in coelomatic fluid in earlier pregnancy. Coelocentesis could be applied in prenatal diagnosis of CSs as well as for other monogenic diseases, at very early stage of pregnancy, if parental mutations are already known.Impact Statement Previous studies utilising coelocentesis for prenatal determination of foetal sex reported variable success ranging from 58% to 95%, because of low total DNA content and presence of maternal cell contamination. This procedure has never been reported for early prenatal diagnosis at 8 weeks of gestation for rare genetically transmitted diseases such as Cockayne's syndrome. This study demonstrates that coelomic fluid sampling combined with well-standardised laboratory procedures can be applied for prenatal diagnosis at eight weeks of gestation for any rare monogenic disease if molecular defects are known. The findings of this study in at risk couples for monogenic diseases investigated by coelocentesis demonstrate that embryo-foetal cell selection from CF allows reliable and early prenatal diagnosis of diseases. This technique is attractive to parents because it provides prenatal diagnosis of genetic disease at least 4 weeks earlier than what can be achieved by the traditional procedures reducing anxiety of parents and provides the option for medical termination of affected cases at 8-10 weeks' gestation, which is less traumatic and safer than second-trimester surgical termination. Further research concerns the possibility to obtain foetal karyotype at eight weeks of gestation and the possibility of intrauterine corrective therapy.
Topics: DNA; Female; Humans; Placenta; Polymerase Chain Reaction; Pregnancy; Prenatal Diagnosis; Sex Factors
PubMed: 35006018
DOI: 10.1080/01443615.2021.2014429 -
Molecular Diagnosis & Therapy Mar 2022Celomic fluid can be considered as an ultra-filtrate of maternal serum, containing a high protein concentration, urea, and many other molecules. It is an important...
BACKGROUND
Celomic fluid can be considered as an ultra-filtrate of maternal serum, containing a high protein concentration, urea, and many other molecules. It is an important transfer interface and a reservoir of nutrients for the embryo. Celomic fluid contains fetal cells that can be used for prenatal diagnosis of monogenic diseases in an earlier gestational period than villocentesis and amniocentesis.
OBJECTIVE
The purpose of this study was to evaluate the characteristics of celomic fluid and to establish a workflow laboratory procedure for very early prenatal diagnosis of monogenic diseases.
METHODS
Three hundred and eighty-five celomatic fluids were collected between the seventh and tenth week of gestation. We sampled 1 mL of celomic fluid in all cases. The embryo-fetal erythroid precursor cells were selected by the anti-CD71 microbead method or by a direct micromanipulator pick-up on the basis of their morphology. We amplified the extracted DNA using a nested polymerase chain reaction. Primers for short tandem repeat amplification were used to perform a quantitative fluorescent polymerase chain reaction evaluation to control maternal contamination.
RESULTS
We observed maternal contamination in 95% of celomic fluids with a range between 5 and 100%. No fetal cells were observed in 0.78% of celomic fluids. The number of fetal cells ranged from a few units to several hundred. Isolation of embryo-fetal erythroblasts selected by the micromanipulator made diagnosis feasible in all cases.
CONCLUSIONS
The selection of fetal cells by a micromanipulator and nested polymerase chain reaction analysis made celomatic fluid suitable for early prenatal diagnosis of monogenic disorders even in the presence of high maternal contamination and few fetal cells. The procedure reported in this study provides the opportunity for the use of celomic fluid sampled by celocentesis as an alternative to chorionic villi sampling and amniocentesis, to allow invasive prenatal diagnosis at a very early stage of pregnancy.
Topics: DNA; Female; Fetus; Humans; Pregnancy; Pregnancy Trimester, First; Prenatal Diagnosis; Workflow
PubMed: 35175567
DOI: 10.1007/s40291-022-00577-3 -
Journal of Obstetrics and Gynaecology... Jun 2020The cost effectiveness of noninvasive prenatal testing (NIPT) has been established for high-risk pregnancies but remains unclear for pregnancies at other risk levels....
OBJECTIVE
The cost effectiveness of noninvasive prenatal testing (NIPT) has been established for high-risk pregnancies but remains unclear for pregnancies at other risk levels. The aim was to assess the cost effectiveness of NIPT in average-risk pregnancies from the perspective of a provincial public payer in Canada.
METHODS
A model was developed to compare traditional prenatal screening (TPS), NIPT as a second-tier test (performed only after a positive TPS result), and NIPT as a first-tier test (performed instead of TPS) for trisomies 21, 18, and 13; sex chromosome aneuploidies; and microdeletions in a hypothetical annual population cohort of average-risk pregnancies (142 000 to 148,000) in Ontario, Canada. A probabilistic analysis was conducted with 5000 repetitions.
RESULTS
Compared with TPS, NIPT as a second-tier test detected more affected fetuses with trisomies 21, 18, and 13 (188 vs. 158), substantially reduced the number of diagnostic tests (i.e., chorionic villus sampling and amniocentesis) performed (660 vs. 3107), and reduced the cost of prenatal screening ($26.7 million vs. $27.6 million) annually. Compared with second-tier NIPT, first-tier NIPT detected an additional 80 cases of trisomies 21, 18, and 13 at an additional cost of $33 million. The incremental cost per additional affected fetus detected was $412 411. Extending first-tier NIPT to include testing for sex chromosome aneuploidies and 22q11.2 deletion would increase the total screening cost.
CONCLUSIONS
NIPT as a second-tier test is cost-saving compared with TPS alone. Compared with second-tier NIPT, first-tier NIPT detects more cases of chromosomal anomalies but at a substantially higher cost.
Topics: Aneuploidy; Cost-Benefit Analysis; Decision Support Techniques; Female; Humans; Noninvasive Prenatal Testing; Ontario; Predictive Value of Tests; Pregnancy; Prenatal Diagnosis; Sex Chromosomes; Trisomy; Ultrasonography, Prenatal
PubMed: 32008974
DOI: 10.1016/j.jogc.2019.12.007